{"id":10634,"date":"2025-07-10T11:57:53","date_gmt":"2025-07-10T03:57:53","guid":{"rendered":"https:\/\/fanyiming.life\/?p=10634"},"modified":"2025-12-21T01:03:30","modified_gmt":"2025-12-20T17:03:30","slug":"%e8%bd%ac%e5%bd%95%e7%bb%84%e7%9a%84%e5%ae%8c%e6%95%b4%e6%80%a7%ef%bc%9a%e4%b8%80%e4%b8%aa%e4%b8%8d%e6%96%ad%e6%89%a9%e5%b1%95%e7%9a%84rna%e4%bf%ae%e5%a4%8d%e4%b8%8e%e6%8d%9f%e4%bc%a4%e5%ba%94","status":"publish","type":"post","link":"https:\/\/fanyiming.life\/?p=10634","title":{"rendered":"\u8f6c\u5f55\u7ec4\u7684\u5b8c\u6574\u6027\uff1a\u4e00\u4e2a\u4e0d\u65ad\u6269\u5c55\u7684RNA\u4fee\u590d\u4e0e\u635f\u4f24\u5e94\u7b54\u7f51\u7edc"},"content":{"rendered":"\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p>By Google Gemini 2.5 Pro Deep research<\/p>\n\n\n\n<p>(\u8c37\u6b4c\u9001\u4e86\u6211\u4e00\u4e2a\u6708\u514d\u8d39\u7684Gemini Pro\uff0c\u771f\u597d\u771f\u597d\uff01<\/p>\n<\/blockquote>\n\n\n\n<h2 class=\"wp-block-heading\">\u5f15\u8a00<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">\u52a8\u6001\u7684\u8f6c\u5f55\u7ec4<\/h3>\n\n\n\n<p>\u5728\u5206\u5b50\u751f\u7269\u5b66\u7684\u7ecf\u5178\u6846\u67b6\u4e2d\uff0cRNA\u901a\u5e38\u88ab\u89c6\u4e3aDNA\u9057\u4f20\u4fe1\u606f\u7684\u77ed\u6682\u3001\u53ef\u6d88\u8017\u7684\u4fe1\u4f7f\u3002\u7136\u800c\uff0c\u8fd9\u4e00\u89c2\u70b9\u6b63\u53d7\u5230\u8d8a\u6765\u8d8a\u591a\u7684\u6311\u6218\u3002\u5927\u91cf\u8bc1\u636e\u8868\u660e\uff0cRNA\uff0c\u5c24\u5176\u662f\u957f\u5bff\u7684RNA\u79cd\u7c7b\uff0c\u5982\u975e\u7f16\u7801RNA\uff08ncRNA\uff09\u4ee5\u53ca\u5b58\u5728\u4e8e\u795e\u7ecf\u5143\u7b49\u6709\u4e1d\u5206\u88c2\u540e\u7ec6\u80de\u4e2d\u7684\u4fe1\u4f7fRNA\uff08mRNA\uff09\uff0c\u662f\u81f3\u5173\u91cd\u8981\u7684\u7ec6\u80de\u7ec4\u5206\uff0c\u5176\u5b8c\u6574\u6027\u5fc5\u987b\u5f97\u5230\u4e3b\u52a8\u7ef4\u6301 <sup>1<\/sup>\u3002\u4e0e\u53cc\u87ba\u65cb\u7ed3\u6784\u4e2d\u53d7\u5230\u4e25\u5bc6\u4fdd\u62a4\u7684DNA\u4e0d\u540c\uff0cRNA\u5206\u5b50\u7531\u4e8e\u5176\u56fa\u6709\u7684\u5316\u5b66\u4e0d\u7a33\u5b9a\u6027\uff08\u6838\u7cd6\u4e0a\u76842&#8242;-\u7f9f\u57fa\uff09\u548c\u5728\u7ec6\u80de\u5185\u66f4\u5e7f\u6cdb\u7684\u5206\u5e03\uff0c\u4f7f\u5176\u66f4\u5bb9\u6613\u53d7\u5230\u5185\u6e90\u6027\u548c\u5916\u6e90\u6027\u635f\u4f24\u56e0\u5b50\u7684\u653b\u51fb\uff0c\u5982\u6d3b\u6027\u6c27\uff08ROS\uff09\u548c\u70f7\u5316\u5242 <sup>1<\/sup>\u3002\u8fd9\u79cd\u8106\u5f31\u6027\u610f\u5473\u7740\uff0c\u7ef4\u6301\u8f6c\u5f55\u7ec4\u7684\u4fdd\u771f\u5ea6\u5bf9\u4e8e\u7ec6\u80de\u7a33\u6001\u3001\u529f\u80fd\u548c\u5b58\u6d3b\u81f3\u5173\u91cd\u8981\u3002<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u65b0\u8303\u5f0f\u7684\u51fa\u73b0<\/h3>\n\n\n\n<p>\u4f20\u7edf\u4e0a\u8ba4\u4e3a\uff0c\u53d7\u635f\u7684RNA\u5206\u5b50\u4f1a\u88ab\u8fc5\u901f\u964d\u89e3\u5e76\u7531\u65b0\u5408\u6210\u7684\u5206\u5b50\u66ff\u4ee3\u3002\u7136\u800c\uff0c\u8d8a\u6765\u8d8a\u591a\u7684\u7814\u7a76\u53d1\u73b0\uff0c\u7ec6\u80de\u8fdb\u5316\u51fa\u4e86\u4e00\u5957\u66f4\u4e3a\u590d\u6742\u7684\u7b56\u7565\uff0c\u4e0d\u4ec5\u5305\u62ec\u964d\u89e3\uff0c\u8fd8\u6d89\u53ca\u5bf9\u53d7\u635fRNA\u7684\u76f4\u63a5\u4fee\u590d\u548c\u7cbe\u5bc6\u7684\u4fe1\u53f7\u5e94\u7b54\u3002\u8fd9\u4e9b\u53d1\u73b0\u50ac\u751f\u4e86\u201cRNA\u635f\u4f24\u5e94\u7b54\u201d\uff08RNA Damage Response, RDR\uff09\u8fd9\u4e00\u65b0\u5174\u6982\u5ff5\u3002RDR\u5e76\u975e\u5355\u4e00\u901a\u8def\uff0c\u800c\u662f\u4e00\u4e2a\u591a\u5c42\u6b21\u7684\u76d1\u89c6\u548c\u7ef4\u62a4\u7cfb\u7edf\uff0c\u5bf9\u4e8e\u9632\u6b62\u9519\u8bef\u86cb\u767d\u7684\u5408\u6210\u3001\u7ef4\u6301\u8c03\u63a7\u7f51\u7edc\u7684\u529f\u80fd\u4ee5\u53ca\u5e94\u5bf9\u7ec6\u80de\u538b\u529b\u81f3\u5173\u91cd\u8981 <sup>3<\/sup>\u3002<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u62a5\u544a\u76ee\u6807<\/h3>\n\n\n\n<p>\u672c\u62a5\u544a\u65e8\u5728\u5168\u9762\u9610\u8ff0RNA\u4fee\u590d\u4e0e\u635f\u4f24\u5e94\u7b54\u9886\u57df\u7684\u5f53\u524d\u8ba4\u77e5\u3002\u62a5\u544a\u5c06\u5206\u4e3a\u4e24\u4e2a\u4e3b\u8981\u90e8\u5206\u3002\u7b2c\u4e00\u90e8\u5206\u5c06\u8be6\u7ec6\u4ecb\u7ecd\u90a3\u4e9b\u4f20\u7edf\u4e0a\u88ab\u8ba4\u4e3a\u662fDNA\u4fee\u590d\u4e13\u5bb6\u7684\u9176\u5bb6\u65cf\uff08\u5982AlkB\u5bb6\u65cf\u3001\u7cd6\u57fa\u5316\u9176\u548c\u8fde\u63a5\u9176\uff09\uff0c\u5982\u4eca\u88ab\u53d1\u73b0\u540c\u6837\u5728RNA\u7ef4\u62a4\u4e2d\u53d1\u6325\u7740\u5173\u952e\u4f5c\u7528\u3002\u6211\u4eec\u5c06\u6df1\u5165\u63a2\u8ba8\u5b83\u4eec\u7684\u540c\u6e90\u7269\u3001\u4f5c\u7528\u5e95\u7269\u548c\u50ac\u5316\u673a\u5236\u3002\u7b2c\u4e8c\u90e8\u5206\u5c06\u501f\u9274\u6210\u719f\u7684DNA\u635f\u4f24\u5e94\u7b54\uff08DNA Damage Response, DDR\uff09\u7406\u8bba\u6846\u67b6\uff0c\u6784\u5efa\u4e00\u4e2a\u65b0\u5174\u7684RDR\u4fe1\u53f7\u7f51\u7edc\u6a21\u578b\u3002\u901a\u8fc7\u5206\u6790\u5176\u5386\u53f2\u53d1\u5c55\u548c\u6838\u5fc3\u903b\u8f91\uff0cDDR\u4e3a\u6211\u4eec\u7406\u89e3RDR\u7684\u611f\u5e94\u5668\u3001\u4fe1\u53f7\u8f6c\u5bfc\u548c\u4e0b\u6e38\u6548\u5e94\u63d0\u4f9b\u4e86\u5b9d\u8d35\u7684\u6982\u5ff5\u84dd\u56fe\u3002\u672c\u62a5\u544a\u5c06\u6574\u5408\u6700\u65b0\u7684\u7814\u7a76\u8fdb\u5c55\uff0c\u63ed\u793aRNA\u4e16\u754c\u4e2d\u8fd9\u4e00\u81f3\u5173\u91cd\u8981\u7684\u8d28\u91cf\u63a7\u5236\u4f53\u7cfb\u7684\u590d\u6742\u6027\u4e0e\u6df1\u523b\u610f\u4e49\u3002<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\" \/>\n\n\n\n<h2 class=\"wp-block-heading\">\u7b2c\u4e00\u90e8\u5206 DNA\u4fee\u590d\u9176\u5728RNA\u4ee3\u8c22\u4e2d\u7684\u201c\u517c\u804c\u201d\u89d2\u8272<\/h2>\n\n\n\n<p>\u957f\u671f\u4ee5\u6765\uff0c\u7ec6\u80de\u5bf9\u6838\u9178\u635f\u4f24\u7684\u9632\u5fa1\u673a\u5236\u7814\u7a76\u4e3b\u8981\u96c6\u4e2d\u5728DNA\u4e0a\u3002\u7136\u800c\uff0c\u8d8a\u6765\u8d8a\u591a\u7684\u8bc1\u636e\u8868\u660e\uff0c\u8bb8\u591a\u7ecf\u5178\u7684DNA\u4fee\u590d\u9176\u5bb6\u65cf\u540c\u6837\u5177\u5907\u8bc6\u522b\u548c\u5904\u7406RNA\u5e95\u7269\u7684\u80fd\u529b\u3002\u8fd9\u79cd\u529f\u80fd\u7684\u4ea4\u53c9\u4e0d\u4ec5\u63ed\u793a\u4e86\u7ec6\u80de\u7ef4\u62a4\u9057\u4f20\u4fe1\u606f\u5b8c\u6574\u6027\u7684\u5e7f\u5ea6\uff0c\u4e5f\u6a21\u7cca\u4e86DNA\u548cRNA\u4ee3\u8c22\u4e4b\u95f4\u7684\u4f20\u7edf\u754c\u9650\u3002\u672c\u90e8\u5206\u5c06\u7cfb\u7edf\u6027\u5730\u68b3\u7406\u8fd9\u4e9b\u201c\u517c\u804c\u201d\u7684DNA\u4fee\u590d\u9176\uff0c\u91cd\u70b9\u4ecb\u7ecdAlkB\u540c\u6e90\u7269\u5bb6\u65cf\u3001\u78b1\u57fa\u5207\u9664\u4fee\u590d\uff08BER\uff09\u901a\u8def\u7684\u5173\u952e\u9176\u4ee5\u53caRNA\u8fde\u63a5\u9176\uff0c\u5e76\u9610\u660e\u5b83\u4eec\u5728RNA\u4fee\u590d\u548c\u8d28\u91cf\u63a7\u5236\u4e2d\u7684\u5177\u4f53\u673a\u5236\u548c\u751f\u7269\u5b66\u610f\u4e49\u3002<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u7b2c\u4e00\u8282 AlkB\u540c\u6e90\u7269\u5bb6\u65cf\uff1a\u6c27\u5316\u53bb\u7532\u57fa\u5316\u7684\u5927\u5e08<\/h3>\n\n\n\n<p>AlkB\u5bb6\u65cf\u4f5c\u4e3a\u4e00\u7c7b\u4f9d\u8d56\u4e8eFe(II)\u548c\u03b1-\u916e\u620a\u4e8c\u9178\uff082-oxoglutarate, 2OG\uff09\u7684\u52a0\u6c27\u9176\uff0c\u5176\u7814\u7a76\u5386\u7a0b\u672c\u8eab\u5c31\u662f\u4eceDNA\u4fee\u590d\u5230RNA\u8868\u89c2\u8f6c\u5f55\u7ec4\u5b66\u8c03\u63a7\u8fd9\u4e00\u8ba4\u77e5\u98de\u8dc3\u7684\u7f29\u5f71\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">1.1 \u8fdb\u5316\u4e0e\u5386\u53f2\u89c6\u89d2<\/h4>\n\n\n\n<p>AlkB\u57fa\u56e0\u7684\u53d1\u73b0\u53ef\u8ffd\u6eaf\u81f31983\u5e74\uff0c\u5f53\u65f6\u5b83\u88ab\u9274\u5b9a\u4e3a\u8d4b\u4e88\u5927\u80a0\u6746\u83cc\uff08<em>E. coli<\/em>\uff09\u62b5\u6297\u7532\u57fa\u5316\u5242\u635f\u4f24\u80fd\u529b\u7684\u4e00\u4e2a\u57fa\u56e0\uff0c\u4f46\u5176\u5177\u4f53\u529f\u80fd\u5728\u968f\u540e\u7684\u4e8c\u5341\u5e74\u91cc\u4e00\u76f4\u662f\u4e2a\u8c1c <sup>8<\/sup>\u3002\u76f4\u52302001\u5e74\uff0c\u901a\u8fc7\u751f\u7269\u4fe1\u606f\u5b66\u5206\u6790\uff0cAravind\u548cKoonin\u624d\u53d6\u5f97\u4e86\u7a81\u7834\u6027\u8fdb\u5c55\u3002\u4ed6\u4eec\u4e0d\u4ec5\u5c06AlkB\u9274\u5b9a\u4e3a2OG-Fe(II)\u52a0\u6c27\u9176\u8d85\u5bb6\u65cf\u7684\u4e00\u5458\uff0c\u8fd8\u6781\u5177\u524d\u77bb\u6027\u5730\u9884\u6d4b\uff0c\u5176\u771f\u6838\u751f\u7269\u540c\u6e90\u7269\u53ef\u80fd\u53c2\u4e0eRNA\u7684\u53bb\u7532\u57fa\u5316\u8fc7\u7a0b <sup>8<\/sup>\u3002\u8fd9\u4e00\u9884\u6d4b\u4e3a\u540e\u7eed\u7684\u7814\u7a76\u6307\u660e\u4e86\u65b9\u5411\uff0c\u5e76\u6700\u7ec8\u88ab\u5b9e\u9a8c\u8bc1\u5b9e\uff0c\u63ed\u793a\u4e86\u8be5\u5bb6\u65cf\u5728DNA\u4fee\u590d\u548cRNA\u4fee\u9970\u8c03\u63a7\u4e2d\u7684\u53cc\u91cd\u6838\u5fc3\u89d2\u8272\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">1.2 \u4eba\u7c7bALKBH\u540c\u6e90\u7269\uff08ALKBH1-8, FTO\uff09\u7684\u8be6\u7ec6\u52d8\u5bdf<\/h4>\n\n\n\n<p>\u4eba\u7c7b\u57fa\u56e0\u7ec4\u7f16\u7801\u4e86\u4e5d\u4e2aAlkB\u7684\u540c\u6e90\u7269\uff0c\u7edf\u79f0\u4e3aALKBH1-8\u548cFTO\uff08fat mass and obesity-associated protein\uff09\u3002\u8fd9\u4e9b\u540c\u6e90\u7269\u5728\u5e95\u7269\u7279\u5f02\u6027\u548c\u751f\u7269\u5b66\u529f\u80fd\u4e0a\u8868\u73b0\u51fa\u663e\u8457\u7684\u591a\u6837\u6027\uff0c\u5f62\u6210\u4e86\u4e00\u4e2a\u529f\u80fd\u5206\u5316\u7684\u9176\u5bb6\u65cf\u3002<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>\u771f\u6b63\u7684DNA\/RNA\u4fee\u590d\u9176<\/strong>\uff1aALKBH2\u548cALKBH3\u88ab\u786e\u8ba4\u4e3a\u771f\u6b63\u7684\u7ec6\u80de\u6838DNA\u4fee\u590d\u9176\u3002\u5b83\u4eec\u80fd\u591f\u6709\u6548\u8865\u507f<em>E. coli<\/em> AlkB\u7684\u7f3a\u9677\uff0c\u4fee\u590d\u7531\u70f7\u5316\u5242\uff08\u5982MMS\uff09\u8bf1\u5bfc\u7684\u635f\u4f24\uff0c\u4e3b\u8981\u5305\u62ec1-\u7532\u57fa\u817a\u560c\u5464\uff08N1-methyladenine, m1A\uff09\u548c3-\u7532\u57fa\u80de\u5627\u5576\uff08N3-methylcytosine, m3C\uff09\u7b49\u635f\u4f24\u78b1\u57fa\u3002ALKBH2\u5bf9\u5355\u94feDNA\uff08ssDNA\uff09\u548c\u53cc\u94feDNA\uff08dsDNA\uff09\u5747\u6709\u6d3b\u6027\uff0c\u800cALKBH3\u5219\u4f18\u5148\u4f5c\u7528\u4e8essDNA\u548cRNA <sup>8<\/sup>\u3002ALKBH3\u5bf9RNA\u5e95\u7269\u7684\u6d3b\u6027\uff0c\u76f4\u63a5\u8bc1\u660e\u4e86DNA\u4fee\u590d\u673a\u5236\u5411RNA\u9886\u57df\u7684\u5ef6\u4f38\uff0c\u5176\u529f\u80fd\u5bf9\u4e8e\u4fdd\u62a4\u7ec6\u80de\u514d\u53d7RNA\u70f7\u5316\u635f\u4f24\u81f3\u5173\u91cd\u8981 <sup>5<\/sup>\u3002<\/li>\n\n\n\n<li><strong>\u8868\u89c2\u8f6c\u5f55\u7ec4\u7684\u201c\u64e6\u9664\u5668\u201d<\/strong>\uff1aALKBH5\u548cFTO\u662f\u76ee\u524d\u7814\u7a76\u6700\u5e7f\u6cdb\u7684RNA\u53bb\u7532\u57fa\u5316\u9176\uff0c\u5b83\u4eec\u7684\u4e3b\u8981\u529f\u80fd\u662f\u53bb\u9664mRNA\u4e0a\u6700\u4e30\u5bcc\u7684\u5185\u90e8\u4fee\u9970\u2014\u2014N6-\u7532\u57fa\u817a\u560c\u5464\uff08N6-methyladenosine, m6A\uff09 <sup>8<\/sup>\u3002m6A\u662f\u4e00\u79cd\u53ef\u9006\u7684\u5316\u5b66\u4fee\u9970\uff0c\u5728\u8c03\u63a7mRNA\u7684\u526a\u63a5\u3001\u7a33\u5b9a\u6027\u3001\u51fa\u6838\u548c\u7ffb\u8bd1\u7b49\u65b9\u9762\u53d1\u6325\u7740\u5173\u952e\u4f5c\u7528\u3002\u56e0\u6b64\uff0cALKBH5\u548cFTO\u7684\u529f\u80fd\u66f4\u504f\u5411\u4e8e\u52a8\u6001\u7684\u57fa\u56e0\u8868\u8fbe\u8c03\u63a7\uff0c\u800c\u975e\u5bf9\u968f\u673a\u635f\u4f24\u7684\u4fee\u590d\u3002\u6b64\u5916\uff0cFTO\u8fd8\u88ab\u53d1\u73b0\u5bf9ssDNA\/RNA\u4e2d\u76843-\u7532\u57fa\u5c3f\u5627\u5576\uff08m3U\uff09\u5177\u6709\u6d3b\u6027 <sup>11<\/sup>\u3002<\/li>\n\n\n\n<li><strong>\u529f\u80fd\u7279\u5316\u4e0e\u591a\u529f\u80fd\u7684\u540c\u6e90\u7269<\/strong>\uff1a\u5176\u4ed6ALKBH\u540c\u6e90\u7269\u5219\u5c55\u73b0\u4e86\u66f4\u4e3a\u7279\u5316\u7684\u529f\u80fd\u3002ALKBH1\u529f\u80fd\u591a\u6837\uff0c\u5176\u5e95\u7269\u6db5\u76d6DNA\u3001RNA\u548c\u7ec4\u86cb\u767dH2A <sup>10<\/sup>\u3002ALKBH8\u5728tRNA\u7684\u6210\u719f\u8fc7\u7a0b\u4e2d\u626e\u6f14\u7740\u5173\u952e\u89d2\u8272\uff0c\u5b83\u50ac\u5316tRNA\u53cd\u5bc6\u7801\u5b50\u6446\u52a8\u4f4d\u4e0a5-\u7532\u6c27\u7fb0\u57fa\u7532\u57fa\u5c3f\u82f7\uff08mcm5U\uff09\u7684\u7f9f\u57fa\u5316\u4fee\u9970 <sup>10<\/sup>\u3002ALKBH4\u7684\u4e3b\u8981\u5e95\u7269\u662f\u808c\u52a8\u86cb\u767d <sup>10<\/sup>\uff0c\u800cALKBH7\u5219\u4f5c\u7528\u4e8e\u7ebf\u7c92\u4f53RNA\u548c\u86cb\u767d\u8d28 <sup>13<\/sup>\u3002ALKBH6\u7684\u529f\u80fd\u5c1a\u4e0d\u5b8c\u5168\u6e05\u695a\uff0c\u4f46\u7814\u7a76\u8868\u660e\u5b83\u5728\u7ef4\u6301\u80f0\u817a\u764c\u7ec6\u80de\u7684\u57fa\u56e0\u7ec4\u7a33\u5b9a\u6027\u65b9\u9762\u81f3\u5173\u91cd\u8981 <sup>10<\/sup>\u3002\u8fd9\u79cd\u529f\u80fd\u4e0a\u7684\u591a\u6837\u5316\uff0c\u6e05\u6670\u5730\u5c55\u793a\u4e86AlkB\u86cb\u767d\u7684\u4fdd\u5b88\u201cjelly-roll\u201d\u6298\u53e0\u7ed3\u6784\u5728\u8fdb\u5316\u8fc7\u7a0b\u4e2d\u5982\u4f55\u88ab\u8c03\u6574\u548c\u6539\u9020\uff0c\u4ee5\u9002\u5e94\u5e7f\u6cdb\u7684\u7ec6\u80de\u4efb\u52a1\u3002<\/li>\n<\/ul>\n\n\n\n<p>\u4e3a\u4e86\u6e05\u6670\u5730\u603b\u7ed3\u8fd9\u4e9b\u590d\u6742\u7684\u4fe1\u606f\uff0c\u4e0b\u8868\u5217\u51fa\u4e86\u4eba\u7c7bAlkB\u540c\u6e90\u7269\u53ca\u5176\u4e3b\u8981\u7684\u6838\u9178\u5e95\u7269\u548c\u529f\u80fd\u3002<\/p>\n\n\n\n<p><strong>\u88681\uff1a\u4eba\u7c7bAlkB\u540c\u6e90\u7269\u53ca\u5176\u6838\u9178\u5e95\u7269\u4e0e\u529f\u80fd<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><td>\u540c\u6e90\u7269<\/td><td>\u4e3b\u8981\u5e95\u7269<\/td><td>\u5173\u952e\u635f\u4f24\/\u4fee\u9970<\/td><td>\u4e3b\u8981\u7ec6\u80de\u4f5c\u7528<\/td><td>\u53c2\u8003\u6587\u732e<\/td><\/tr><\/thead><tbody><tr><td><strong>ALKBH1<\/strong><\/td><td>ssDNA, dsDNA, RNA, \u7ec4\u86cb\u767dH2A<\/td><td>m1A, m3C, m6A<\/td><td>DNA\/RNA\u53bb\u7532\u57fa\u5316, \u7ec4\u86cb\u767d\u53bb\u7532\u57fa\u5316<\/td><td><sup>10<\/sup><\/td><\/tr><tr><td><strong>ALKBH2<\/strong><\/td><td>dsDNA &gt; ssDNA<\/td><td>m1A, m3C, \u03f5A<\/td><td>DNA\u70f7\u5316\u635f\u4f24\u4fee\u590d<\/td><td><sup>8<\/sup><\/td><\/tr><tr><td><strong>ALKBH3<\/strong><\/td><td>ssDNA, RNA<\/td><td>m1A, m3C<\/td><td>DNA\/RNA\u70f7\u5316\u635f\u4f24\u4fee\u590d<\/td><td><sup>11<\/sup><\/td><\/tr><tr><td><strong>ALKBH4<\/strong><\/td><td>\u808c\u52a8\u86cb\u767d<\/td><td>K84me1<\/td><td>\u86cb\u767d\u8d28\u53bb\u7532\u57fa\u5316<\/td><td><sup>10<\/sup><\/td><\/tr><tr><td><strong>ALKBH5<\/strong><\/td><td>mRNA, lncRNA<\/td><td>m6A<\/td><td>RNA\u53bb\u7532\u57fa\u5316 (\u8868\u89c2\u8f6c\u5f55\u7ec4\u8c03\u63a7)<\/td><td><sup>8<\/sup><\/td><\/tr><tr><td><strong>ALKBH6<\/strong><\/td><td>DNA<\/td><td>\u672a\u660e\u786e, \u53c2\u4e0e\u57fa\u56e0\u7ec4\u7a33\u5b9a<\/td><td>DNA\u635f\u4f24\u4fee\u590d<\/td><td><sup>13<\/sup><\/td><\/tr><tr><td><strong>ALKBH7<\/strong><\/td><td>mt-RNA, \u86cb\u767d\u8d28<\/td><td>m1A, m22G<\/td><td>\u7ebf\u7c92\u4f53RNA\u4fee\u9970, \u86cb\u767d\u8d28\u4fee\u9970<\/td><td><sup>13<\/sup><\/td><\/tr><tr><td><strong>ALKBH8<\/strong><\/td><td>tRNA<\/td><td>mcm5U<\/td><td>tRNA\u6210\u719f<\/td><td><sup>10<\/sup><\/td><\/tr><tr><td><strong>FTO<\/strong><\/td><td>mRNA, lncRNA, snRNA, tRNA<\/td><td>m6A, m6Am, m1A, m3U<\/td><td>RNA\u53bb\u7532\u57fa\u5316 (\u8868\u89c2\u8f6c\u5f55\u7ec4\u8c03\u63a7)<\/td><td><sup>8<\/sup><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h4 class=\"wp-block-heading\">1.3 \u673a\u5236\u4e0a\u7684\u4e8c\u5206\u6cd5\uff1aFTO\u4e0eALKBH5\u50ac\u5316\u7b56\u7565\u7684\u5bf9\u6bd4<\/h4>\n\n\n\n<p>\u5c3d\u7ba1FTO\u548cALKBH5\u90fd\u80fd\u591f\u50ac\u5316m6A\u7684\u53bb\u7532\u57fa\u5316\uff0c\u4f46\u5b83\u4eec\u7684\u50ac\u5316\u673a\u5236\u3001\u53cd\u5e94\u4ea7\u7269\u548c\u52a8\u529b\u5b66\u7279\u5f81\u5374\u5b58\u5728\u7740\u6df1\u523b\u7684\u5dee\u5f02\uff0c\u8fd9\u53cd\u6620\u4e86\u5b83\u4eec\u5728\u7ec6\u80de\u5185\u53ef\u80fd\u626e\u6f14\u7740\u4e0d\u540c\u7684\u8c03\u63a7\u89d2\u8272\u3002<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>FTO\u7684\u7ecf\u5178\u901a\u8def<\/strong>\uff1aFTO\u9075\u5faa\u4e00\u79cd\u4f20\u7edf\u7684\u6c27\u5316\u53bb\u7532\u57fa\u5316\u9014\u5f84\u3002\u5b83\u9996\u5148\u5c06m6A\u6c27\u5316\u4e3a\u4e00\u4e2a\u76f8\u5bf9\u7a33\u5b9a\u7684\u4e2d\u95f4\u4ea7\u7269\u2014\u2014N6-\u7f9f\u7532\u57fa\u817a\u560c\u5464\uff08N6-hydroxymethyladenosine, hm6A\uff09\u3002\u968f\u540e\uff0chm6A\u4f1a\u7f13\u6162\u5730\u5206\u89e3\uff0c\u91ca\u653e\u51fa\u7532\u919b\uff08formaldehyde, FA\uff09\u548c\u672a\u4fee\u9970\u7684\u817a\u560c\u5464\uff08A\uff09 <sup>16<\/sup>\u3002\u8fd9\u79cd\u5206\u6b65\u53cd\u5e94\u7684\u52a8\u529b\u5b66\u7279\u5f81\u610f\u5473\u7740hm6A\u672c\u8eab\u53ef\u80fd\u4f5c\u4e3a\u4e00\u79cd\u65b0\u7684\u3001\u5177\u6709\u751f\u7269\u5b66\u529f\u80fd\u7684RNA\u4fee\u9970\u5f62\u5f0f\u5b58\u5728\u3002<\/li>\n\n\n\n<li><strong>ALKBH5\u7684\u65b0\u578b\u5171\u4ef7\u673a\u5236<\/strong>\uff1a\u4e0eFTO\u4e0d\u540c\uff0cALKBH5\u7684\u50ac\u5316\u8fc7\u7a0b\u5c55\u73b0\u51fa\u4e00\u79cd\u524d\u6240\u672a\u6709\u7684\u9ad8\u6548\u673a\u5236\u3002\u7814\u7a76\u8868\u660e\uff0cALKBH5\u80fd\u591f\u76f4\u63a5\u5c06m6A\u8f6c\u5316\u4e3a\u817a\u560c\u5464\uff08A\uff09\uff0c\u5e76\u5feb\u901f\u3001\u540c\u6b65\u5730\u91ca\u653e\u7532\u919b\uff0c\u6574\u4e2a\u8fc7\u7a0b\u4ec5\u9700\u4e00\u6b21\u6c27\u5316\u53cd\u5e94 <sup>16<\/sup>\u3002\u8fd9\u79cd\u9ad8\u6548\u7684\u76f4\u63a5\u53bb\u7532\u57fa\u5316\u662f\u901a\u8fc7\u4e00\u4e2a\u72ec\u7279\u7684\u5171\u4ef7\u50ac\u5316\u673a\u5236\u5b9e\u73b0\u7684\u3002\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76\u8fdb\u4e00\u6b65\u63ed\u793a\uff0cALKBH5\u6d3b\u6027\u4e2d\u5fc3\u7684\u4e00\u4e2a\u7531Lys132\u548cTyr139\u7b49\u6b8b\u57fa\u6784\u6210\u7684\u8d28\u5b50\u7a7f\u68ad\u7f51\u7edc\uff0c\u5bf9\u4e8e\u50ac\u5316\u8fd9\u4e00\u5feb\u901f\u53cd\u5e94\u81f3\u5173\u91cd\u8981\uff0c\u800c\u8fd9\u4e00\u7ed3\u6784\u5728FTO\u4e2d\u5e76\u4e0d\u4fdd\u5b88 <sup>18<\/sup>\u3002\u5b9e\u9a8c\u8bc1\u636e\u4e5f\u652f\u6301\u4e86\u8fd9\u4e00\u70b9\uff1a\u5c06ALKBH5\u7684Lys132\u7a81\u53d8\u4e3a\u8c37\u6c28\u9170\u80fa\uff08K132Q\uff09\uff0c\u4f1a\u7834\u574f\u5176\u5171\u4ef7\u50ac\u5316\u673a\u5236\uff0c\u4f7f\u5176\u53cd\u5e94\u6a21\u5f0f\u53d8\u5f97\u4e0eFTO\u7c7b\u4f3c <sup>16<\/sup>\u3002<\/li>\n<\/ul>\n\n\n\n<p>\u8fd9\u79cd\u673a\u5236\u4e0a\u7684\u5206\u6b67\u5177\u6709\u6df1\u8fdc\u7684\u751f\u7269\u5b66\u610f\u4e49\u3002ALKBH5\u7684\u5feb\u901f\u53bb\u7532\u57fa\u5316\u548c\u7532\u919b\u91ca\u653e\uff0c\u4f7f\u5176\u6210\u4e3a\u7ec6\u80de\u5185\u7532\u919b\u7684\u4e00\u4e2a\u6f5c\u5728\u5185\u6e90\u6027\u6765\u6e90\uff0c\u800c\u7532\u919b\u662f\u4e00\u79cd\u5177\u6709\u9057\u4f20\u6bd2\u6027\u7684\u4e00\u78b3\u5355\u4f4d\u3002\u56e0\u6b64\uff0c\u8fd9\u4e24\u79cd\u9176\u4e0d\u4ec5\u5728\u5e95\u7269\u504f\u597d\u548c\u7ec6\u80de\u5b9a\u4f4d\u4e0a\u4e0d\u540c\uff0c\u5b83\u4eec\u50ac\u5316\u53cd\u5e94\u7684\u901f\u7387\u548c\u4ea7\u7269\u4e5f\u4e0d\u540c\uff0c\u8fd9\u4e3a\u7ec6\u80de\u63d0\u4f9b\u4e86\u4e24\u79cd\u622a\u7136\u4e0d\u540c\u7684m6A\u8c03\u63a7\u6a21\u5f0f\uff1aFTO\u53ef\u80fd\u4ecb\u5bfc\u4e00\u79cd\u66f4\u4e3a\u7cbe\u7ec6\u3001\u5206\u6b65\u7684\u8c03\u63a7\uff0c\u800cALKBH5\u5219\u6267\u884c\u4e00\u79cd\u66f4\u5feb\u901f\u3001\u66f4\u5f7b\u5e95\u7684\u201c\u64e6\u9664\u201d\u64cd\u4f5c\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">1.4 \u75c5\u7406\u751f\u7406\u5b66\u5f71\u54cd<\/h4>\n\n\n\n<p>AlkB\u5bb6\u65cf\u6210\u5458\uff0c\u5c24\u5176\u662fFTO\u548cALKBH5\u7684\u5931\u8c03\uff0c\u4e0e\u591a\u79cd\u4eba\u7c7b\u75be\u75c5\u5bc6\u5207\u76f8\u5173\uff0c\u5176\u4e2d\u6700\u5f15\u4eba\u6ce8\u76ee\u7684\u662f\u5728\u764c\u75c7\u4e2d\u7684\u4f5c\u7528\u3002\u5b83\u4eec\u5728\u4e0d\u540c\u7c7b\u578b\u7684\u764c\u75c7\u4e2d\u65e2\u53ef\u4f5c\u4e3a\u764c\u57fa\u56e0\u4e5f\u53ef\u4f5c\u4e3a\u6291\u764c\u57fa\u56e0\uff0c\u8fd9\u53d6\u51b3\u4e8e\u7ec6\u80de\u7684\u7c7b\u578b\u548c\u5177\u4f53\u7684\u5206\u5b50\u73af\u5883\u3002\u4f8b\u5982\uff0c\u5b83\u4eec\u901a\u8fc7\u8c03\u63a7\u4e0b\u6e38\u9776\u57fa\u56e0\uff08\u5982YAP\u3001MYC\uff09\u7684m6A\u6c34\u5e73\uff0c\u5f71\u54cd\u5173\u952e\u7684\u4fe1\u53f7\u901a\u8def\uff08\u5982Wnt\u3001AKT\u3001NF-\u03baB\uff09\uff0c\u4ece\u800c\u53c2\u4e0e\u8c03\u63a7\u764c\u7ec6\u80de\u7684\u589e\u6b96\u3001\u5b58\u6d3b\u3001\u8f6c\u79fb\u548c\u6cbb\u7597\u62b5\u6297 <sup>9<\/sup>\u3002\u8fd9\u79cd\u5728\u75be\u75c5\u4e2d\u7684\u5173\u952e\u4f5c\u7528\uff0c\u4f7f\u5176\u6210\u4e3a\u6781\u5177\u5438\u5f15\u529b\u7684\u836f\u7269\u5f00\u53d1\u9776\u70b9\u3002\u76ee\u524d\uff0c\u9488\u5bf9FTO\u548cALKBH5\u7684\u5c0f\u5206\u5b50\u6291\u5236\u5242\u7684\u7814\u53d1\u6b63\u5728\u79ef\u6781\u8fdb\u884c\u4e2d\uff0c\u5e76\u5df2\u5728\u4e34\u5e8a\u524d\u6a21\u578b\u4e2d\u663e\u793a\u51fa\u6297\u80bf\u7624\u6f5c\u529b <sup>20<\/sup>\u3002<\/p>\n\n\n\n<p>AlkB\u5bb6\u65cf\u7684\u7814\u7a76\u6e05\u6670\u5730\u5c55\u793a\u4e86\u201cRNA\u4fee\u590d\u201d\u8fd9\u4e00\u6982\u5ff5\u7684\u5e7f\u9614\u5185\u6db5\u3002\u5b83\u5e76\u975e\u4e00\u4e2a\u5355\u4e00\u7684\u8fc7\u7a0b\uff0c\u800c\u662f\u6db5\u76d6\u4e86\u4e00\u4e2a\u4ece\u7ecf\u5178\u7684\u635f\u4f24\u9006\u8f6c\u5230\u52a8\u6001\u7684\u8c03\u63a7\u6027\u4fee\u9970\u7684\u8fde\u7eed\u8c31\u3002\u4e00\u65b9\u9762\uff0cALKBH3\u7b49\u9176\u5bf9m1A\u548cm3C\u8fd9\u7c7b\u5177\u6709\u660e\u786e\u7ec6\u80de\u6bd2\u6027\u7684\u635f\u4f24\u8fdb\u884c\u4fee\u590d\uff0c\u8fd9\u662f\u4e00\u79cd\u5178\u578b\u7684\u635f\u4f24\u63a7\u5236\uff08damage control\uff09\u529f\u80fd\uff0c\u65e8\u5728\u6062\u590dRNA\u5206\u5b50\u7684\u5316\u5b66\u7ed3\u6784\u548c\u751f\u7269\u5b66\u529f\u80fd\uff0c\u9632\u6b62\u7ffb\u8bd1\u505c\u6ede\u548c\u7ec6\u80de\u6b7b\u4ea1 <sup>11<\/sup>\u3002\u53e6\u4e00\u65b9\u9762\uff0cFTO\u548cALKBH5\u7b49\u9176\u5219\u8c03\u63a7m6A\u8fd9\u4e00\u53ef\u9006\u7684\u8868\u89c2\u8f6c\u5f55\u7ec4\u6807\u8bb0\uff0c\u53c2\u4e0e\u5230\u590d\u6742\u7684\u57fa\u56e0\u8868\u8fbe\u8c03\u63a7\u7f51\u7edc\u4e2d\uff0c\u8fd9\u662f\u4e00\u79cd\u4e3b\u52a8\u7684\u4fe1\u53f7\u8c03\u8282\uff08signal regulation\uff09\u529f\u80fd <sup>8<\/sup>\u3002\u540c\u4e00\u4e2a\u9176\u5bb6\u65cf\uff0c\u5229\u7528\u76f8\u540c\u7684\u6838\u5fc3\u50ac\u5316\u5316\u5b66\uff08\u6c27\u5316\u53bb\u7532\u57fa\u5316\uff09\uff0c\u5374\u88ab\u8fdb\u5316\u7528\u4e8e\u4e24\u79cd\u622a\u7136\u4e0d\u540c\u7684\u751f\u7269\u5b66\u76ee\u7684\u3002\u8fd9\u8868\u660e\uff0c\u5728\u7ec6\u80de\u5c42\u9762\uff0c\u201c\u635f\u4f24\u201d\u4e0e\u201c\u4fe1\u53f7\u201d\u7684\u754c\u9650\u662f\u6a21\u7cca\u4e14\u4f9d\u8d56\u4e8e\u5177\u4f53\u60c5\u5883\u7684\uff0c\u5176\u5173\u952e\u533a\u522b\u5728\u4e8e\u4e00\u4e2a\u4fee\u9970\u662f\u968f\u673a\u4ea7\u751f\u7684\u6709\u5bb3\u53d8\u5316\uff0c\u8fd8\u662f\u4e00\u4e2a\u88ab\u7cbe\u786e\u8c03\u63a7\u7684\u7a0b\u5e8f\u5316\u6807\u8bb0\u3002<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u7b2c\u4e8c\u8282 \u78b1\u57fa\u5207\u9664\u4fee\u590d\uff08BER\uff09\u673a\u5668\uff1a\u4e00\u79cd\u201cRNA\u51c0\u5316\u201d\u670d\u52a1<\/h3>\n\n\n\n<p>\u78b1\u57fa\u5207\u9664\u4fee\u590d\uff08Base Excision Repair, BER\uff09\u662f\u7ec6\u80de\u4e2d\u4fee\u590d\u7531\u6c27\u5316\u3001\u70f7\u5316\u6216\u81ea\u53d1\u6c34\u89e3\u5f15\u8d77\u7684\u975e\u5927\u4f53\u79efDNA\u78b1\u57fa\u635f\u4f24\u7684\u4e3b\u8981\u9014\u5f84\u3002\u8fd1\u5e74\u6765\uff0c\u8d8a\u6765\u8d8a\u591a\u7684\u8bc1\u636e\u8868\u660e\uff0c\u8fd9\u4e00\u7ecf\u5178\u7684DNA\u4fee\u590d\u901a\u8def\u4e2d\u7684\u5173\u952e\u9176\u4e5f\u80fd\u4f5c\u7528\u4e8eRNA\uff0c\u6267\u884c\u4e00\u79cd\u88ab\u79f0\u4e3a\u201cRNA\u51c0\u5316\u201d\u7684\u8d28\u91cf\u63a7\u5236\u529f\u80fd\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">2.1 \u7ecf\u5178BER\u901a\u8def\u7b80\u8ff0<\/h4>\n\n\n\n<p>\u5728DNA\u4e2d\uff0cBER\u901a\u8def\u901a\u5e38\u6309\u4ee5\u4e0b\u6b65\u9aa4\u8fdb\u884c\uff1a\u9996\u5148\uff0c\u4e00\u79cd\u635f\u4f24\u7279\u5f02\u6027\u7684DNA\u7cd6\u57fa\u5316\u9176\u8bc6\u522b\u5e76\u5207\u9664\u53d7\u635f\u7684\u78b1\u57fa\uff0c\u5728DNA\u94fe\u4e0a\u7559\u4e0b\u4e00\u4e2a\u8131\u560c\u5464\/\u8131\u5627\u5576\uff08AP\uff09\u4f4d\u70b9\u3002\u63a5\u7740\uff0cAP\u6838\u9178\u5185\u5207\u9176\uff08\u5982APE1\uff09\u5728AP\u4f4d\u70b9\u76845&#8217;\u7aef\u5207\u65ad\u78f7\u9178\u4e8c\u916f\u9aa8\u67b6\u3002\u6700\u540e\uff0cDNA\u805a\u5408\u9176\u586b\u8865\u7f3a\u53e3\uff0cDNA\u8fde\u63a5\u9176\u5c01\u53e3\uff0c\u5b8c\u6210\u4fee\u590d\u8fc7\u7a0b <sup>23<\/sup>\u3002\u7406\u89e3\u8fd9\u4e00\u57fa\u672c\u6d41\u7a0b\u662f\u63a2\u8ba8\u5176\u5728RNA\u4ee3\u8c22\u4e2d\u53ef\u80fd\u4f5c\u7528\u7684\u57fa\u7840\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">2.2 RNA\u7cd6\u57fa\u5316\u9176\uff1a\u8bc6\u522b\u5e76\u5207\u9664\u53d7\u635f\u7684\u6838\u7cd6\u6838\u82f7\u9178<\/h4>\n\n\n\n<p>\u6709\u8bc1\u636e\u8868\u660e\uff0c\u4e00\u4e9bDNA\u7cd6\u57fa\u5316\u9176\u5177\u6709\u5904\u7406RNA\u5e95\u7269\u7684\u80fd\u529b\uff0c\u8fd9\u4e3aRNA\u635f\u4f24\u7684\u8bc6\u522b\u63d0\u4f9b\u4e86\u7b2c\u4e00\u9053\u9632\u7ebf\u3002<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>SMUG1<\/strong>\uff1a\u5355\u94fe\u9009\u62e9\u6027\u5355\u529f\u80fd\u5c3f\u5627\u5576-DNA\u7cd6\u57fa\u5316\u91761\uff08SMUG1\uff09\u7684\u5e95\u7269\u8c31\u76f8\u5f53\u5e7f\u6cdb\u3002\u9664\u4e86\u4eceDNA\u4e2d\u5207\u9664\u5c3f\u5627\u5576\u5916\uff0c\u5b83\u8fd8\u80fd\u8bc6\u522b\u5e76\u5207\u9664RNA\u4e2d\u7684\u591a\u79cd\u4fee\u9970\u78b1\u57fa\uff0c\u5305\u62ec5-\u7f9f\u7532\u57fa\u5c3f\u82f7\uff085hmU\uff09\u548c\u5e7f\u6cdb\u4f7f\u7528\u7684\u5316\u7597\u836f\u72695-\u6c1f\u5c3f\u5627\u5576\uff085-FU\uff09 <sup>26<\/sup>\u3002\u5728\u7f3a\u4e4fSMUG1\u7684\u7ec6\u80de\u4e2d\uff0c\u7814\u7a76\u4eba\u5458\u89c2\u5bdf\u5230\u672a\u6210\u719f\u7684rRNA\u5206\u5b50\u6c34\u5e73\u5347\u9ad8\uff0c\u5e76\u4e14\u6210\u719frRNA\u4e2d5hmU\u7684\u542b\u91cf\u663e\u8457\u79ef\u7d2f\u3002\u8fd9\u4e9b\u53d1\u73b0\u6709\u529b\u5730\u8868\u660e\uff0cSMUG1\u53c2\u4e0e\u4e86rRNA\u7684\u8d28\u91cf\u63a7\u5236\u8fc7\u7a0b\uff0c\u53ef\u80fd\u901a\u8fc7\u53bb\u9664\u5f02\u5e38\u4fee\u9970\u6765\u6807\u8bb0\u53d7\u635f\u7684rRNA\u5206\u5b50 <sup>27<\/sup>\u3002<\/li>\n\n\n\n<li><strong>NEIL1\/OGG1<\/strong>\uff1aNEIL1\u662f\u4e00\u79cd\u80fd\u591f\u53bb\u9664\u591a\u79cd\u6c27\u5316\u635f\u4f24\u78b1\u57fa\u7684DNA\u7cd6\u57fa\u5316\u9176 <sup>28<\/sup>\u3002\u8003\u8651\u5230RNA\u6bd4DNA\u66f4\u5bb9\u6613\u53d7\u5230\u6c27\u5316\u635f\u4f24\uff0c\u7ec6\u80de\u5185\u4f1a\u4ea7\u751f\u5927\u91cf\u7684\u6c27\u5316RNA\u635f\u4f24\uff0c\u59828-\u6c27\u4ee3\u9e1f\u560c\u5464\uff088-oxoguanine, 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APE1\uff1a\u5728\u8131\u78b1\u57faRNA\u7684\u6838\u9178\u5185\u5207\u4e2d\u7684\u65b0\u89d2\u8272<\/h4>\n\n\n\n<p>\u7cd6\u57fa\u5316\u9176\u5207\u9664\u78b1\u57fa\u540e\uff0c\u7559\u4e0b\u7684AP\u4f4d\u70b9\u662fBER\u901a\u8def\u7684\u5171\u540c\u4e2d\u95f4\u4ea7\u7269\u3002\u4e00\u4e2a\u91cc\u7a0b\u7891\u5f0f\u7684\u53d1\u73b0\u662f\uff0c\u4eba\u7c7b\u4e3b\u8981\u7684AP\u6838\u9178\u5185\u5207\u9176APE1\u4e0d\u4ec5\u80fd\u5207\u5272DNA\u4e2d\u7684AP\u4f4d\u70b9\uff0c\u8fd8\u80fd\u6709\u6548\u5207\u5272\u5b58\u5728\u4e8e\u5355\u94feRNA\uff08ssRNA\uff09\u4ee5\u53caDNA\/RNA\u6742\u5408\u94fe\u4e2d\u7684AP\u4f4d\u70b9 <sup>25<\/sup>\u3002\u8fd9\u4e00\u529f\u80fd\u88ab\u6070\u5f53\u5730\u79f0\u4e3a\u201cRNA\u51c0\u5316\u201d\uff08RNA 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\u4e00\u4e2a\u72ec\u7279\u7684\u8c03\u63a7\u73af\u8def\uff1aNEIL1\u7684RNA\u7f16\u8f91<\/h4>\n\n\n\n<p>\u5728RNA\u4e0eDNA\u4fee\u590d\u7684\u4ea4\u6c47\u70b9\u4e0a\uff0c\u5b58\u5728\u4e00\u4e2a\u5c24\u4e3a\u7cbe\u5999\u7684\u8c03\u63a7\u73af\u8def\uff1aDNA\u4fee\u590d\u9176NEIL1\u81ea\u8eab\u7684pre-mRNA\u5c31\u662fRNA\u7f16\u8f91\u7684\u9776\u6807\u3002\u817a\u82f7\u8131\u6c28\u9176ADAR1\u80fd\u591f\u5bf9NEIL1\u7684pre-mRNA\u8fdb\u884cA-to-I\uff08\u817a\u82f7\u5230\u808c\u82f7\uff09\u7684\u7f16\u8f91\uff0c\u8fd9\u4e00\u7f16\u8f91\u4e8b\u4ef6\u5bfc\u81f4\u7ffb\u8bd1\u51fa\u7684NEIL1\u86cb\u767d\u5728\u5176\u635f\u4f24\u8bc6\u522b\u73af\uff08lesion recognition loop\uff09\u4e2d\u53d1\u751f\u4e00\u4e2a\u5173\u952e\u7684\u6c28\u57fa\u9178\u53d8\u5316\uff08\u8d56\u6c28\u9178\u53d8\u4e3a\u7cbe\u6c28\u9178\uff09\u3002\u4ee4\u4eba\u60ca\u8bb6\u7684\u662f\uff0c\u8fd9\u79cd\u5fae\u5c0f\u7684\u6539\u53d8\u6781\u5927\u5730\u91cd\u5851\u4e86NEIL1\u7684\u50ac\u5316\u6d3b\u6027\u548c\u5e95\u7269\u7279\u5f02\u6027\u3002\u4e0e\u672a\u7ecf\u7f16\u8f91\u7684\u91ce\u751f\u578b\u86cb\u767d\u76f8\u6bd4\uff0c\u7f16\u8f91\u540e\u7684NEIL1\u4fee\u590d\u80f8\u817a\u5627\u5576\u4e59\u4e8c\u9187\uff08thymine glycol\uff09\u7684\u6548\u7387\u964d\u4f4e\u4e8630\u500d\uff0c\u800c\u4fee\u590d\u9e1f\u560c\u5464\u4e8c\u5185\u9170\u8132\uff08guanidinohydantoin\uff09\u7684\u6548\u7387\u5219\u63d0\u9ad8\u4e86\u8fd13\u500d <sup>28<\/sup>\u3002\u8fd9\u6784\u6210\u4e86\u4e00\u4e2a\u524d\u6240\u672a\u6709\u7684\u8c03\u63a7\u673a\u5236\uff0c\u5373\u7ec6\u80de\u901a\u8fc7RNA\u5c42\u9762\u7684\u52a0\u5de5\uff0c\u76f4\u63a5\u3001\u52a8\u6001\u5730\u8c03\u6574\u4e86\u4e00\u79cd\u6838\u5fc3DNA\/RNA\u4fee\u590d\u9176\u7684\u529f\u80fd\uff0c\u4ee5\u9002\u5e94\u4e0d\u540c\u7684\u635f\u4f24\u8c31\u6216\u7ec6\u80de\u72b6\u6001\u3002<\/p>\n\n\n\n<p>BER\u673a\u5668\u5728RNA\u4ee3\u8c22\u4e2d\u7684\u53c2\u4e0e\u63ed\u793a\u4e86\u4e00\u79cd\u4e0eAlkB\u5bb6\u65cf\u76f4\u63a5\u4fee\u590d\u622a\u7136\u4e0d\u540c\u7684\u7b56\u7565\u3002AlkB\u9176\u901a\u8fc7\u6c27\u5316\u53bb\u7532\u57fa\u5316\u76f4\u63a5\u5c06\u635f\u4f24\u78b1\u57fa\u6062\u590d\u4e3a\u6b63\u5e38\u78b1\u57fa\uff0c\u4ece\u800c\u4fee\u590dRNA\u5206\u5b50\u672c\u8eab\u3002\u7136\u800c\uff0cBER\u901a\u8def\u7684\u4f5c\u7528\u65b9\u5f0f\u2014\u2014\u7cd6\u57fa\u5316\u9176\u5207\u9664\u78b1\u57fa\uff0c\u968f\u540e\u7531APE1\u5207\u5272\u78f7\u9178\u4e8c\u916f\u9aa8\u67b6\u2014\u2014\u5728RNA\u4e0a\u4ea7\u751f\u4e86\u4e00\u4e2a\u65ad\u88c2\u7684\u94fe\u3002\u4e0eDNA\u4e0d\u540c\uff0cRNA\u901a\u5e38\u662f\u5355\u94fe\u5206\u5b50\uff0c\u7f3a\u4e4f\u7528\u4e8e\u6a21\u677f\u6307\u5bfc\u5408\u6210\u7684\u4e92\u8865\u94fe <sup>5<\/sup>\u3002\u56e0\u6b64\uff0c\u4e00\u4e2a\u88ab\u5207\u5f00\u7684RNA\u5206\u5b50\u6700\u53ef\u80fd\u7684\u547d\u8fd0\u4e0d\u662f\u88ab\u8fde\u63a5\u4fee\u590d\uff0c\u800c\u662f\u88ab\u7ec6\u80de\u5185\u7684\u6838\u9178\u5916\u5207\u9176\u8fc5\u901f\u964d\u89e3 <sup>5<\/sup>\u3002\u8fd9\u8868\u660e\uff0cBER\u9176\u5728RNA\u4e0a\u7684\u201c\u517c\u804c\u201d\u529f\u80fd\uff0c\u5176\u4e3b\u8981\u76ee\u7684\u5e76\u975e\u4fee\u590dRNA\u5206\u5b50\u4ee5\u6062\u590d\u5176\u529f\u80fd\uff0c\u800c\u662f\u8bc6\u522b\u5e76\u6807\u8bb0\u8fd9\u4e9b\u53d7\u635f\u5206\u5b50\uff0c\u542f\u52a8\u5b83\u4eec\u7684\u6e05\u9664\u7a0b\u5e8f\u3002\u8fd9\u662f\u4e00\u79cd\u4e3b\u52a8\u7684\u8d28\u91cf\u63a7\u5236\u673a\u5236\uff0c\u53ef\u4ee5\u88ab\u89c6\u4e3a\u4e00\u79cd\u201cRNA\u51c0\u5316\u201d\uff0c\u5176\u6838\u5fc3\u5728\u4e8e\u201c\u6e05\u9664\u201d\u800c\u975e\u201c\u4fee\u590d\u201d\uff0c\u4ece\u800c\u786e\u4fdd\u8f6c\u5f55\u672c\u6c60\u7684\u6574\u4f53\u8d28\u91cf\uff0c\u9632\u6b62\u9519\u8bef\u4fe1\u606f\u7684\u4f20\u9012\u3002<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u7b2c\u4e09\u8282 RNA\u8fde\u63a5\u9176\uff1a\u4fee\u590d\u65ad\u88c2\u7684\u94fe<\/h3>\n\n\n\n<p>\u4e0e\u901a\u8fc7\u53bb\u9664\u5355\u4e2a\u53d7\u635f\u78b1\u57fa\u8fdb\u884c\u4fee\u590d\u4e0d\u540c\uff0cRNA\u8fde\u63a5\u9176\u8d1f\u8d23\u4fee\u590dRNA\u94fe\u7684\u65ad\u88c2\uff0c\u8fd9\u662f\u7ef4\u6301RNA\u7ed3\u6784\u548c\u529f\u80fd\u5b8c\u6574\u6027\u7684\u6700\u540e\u4e00\u9053\u9632\u7ebf\u3002\u7ec6\u80de\u5185\u5b58\u5728\u7740\u591a\u79cdRNA\u8fde\u63a5\u9176\uff0c\u5b83\u4eec\u5728\u751f\u7406\u8fc7\u7a0b\uff08\u5982tRNA\u526a\u63a5\uff09\u548c\u5e94\u6fc0\u53cd\u5e94\u4e2d\u90fd\u53d1\u6325\u7740\u5173\u952e\u4f5c\u7528\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">3.1 \u5f25\u5408\u7f3a\u53e3\uff1a\u4e24\u79cd\u4e0d\u540c\u7684\u8fde\u63a5\u5316\u5b66<\/h4>\n\n\n\n<p>\u7ec6\u80de\u8fdb\u5316\u51fa\u4e86\u81f3\u5c11\u4e24\u79cd\u4e3b\u8981\u7684RNA\u8fde\u63a5\u5316\u5b66\u673a\u5236\uff0c\u5b83\u4eec\u5728\u80fd\u91cf\u6765\u6e90\u3001\u5e95\u7269\u672b\u7aef\u548c\u50ac\u5316\u673a\u7406\u4e0a\u5404\u4e0d\u76f8\u540c\u3002<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>\u7ecf\u5178\u7684ATP\u4f9d\u8d56\u6027\u8fde\u63a5\u9176<\/strong>\uff1a\u8fd9\u7c7b\u9176\uff0c\u5982\u566c\u83cc\u4f53T4\u7684Rnl1\uff0c\u662f\u7814\u7a76\u5f97\u6700\u4e3a\u900f\u5f7b\u7684RNA\u8fde\u63a5\u9176\u3002\u5b83\u4eec\u50ac\u53163&#8242;-\u7f9f\u57fa\uff083&#8242;-OH\uff09\u548c5&#8242;-\u78f7\u9178\uff085&#8242;-PO4\uff09\u672b\u7aef\u7684\u8fde\u63a5\u3002\u7136\u800c\uff0c\u8bb8\u591a\u7ec6\u80de\u5185\u7684\u6838\u7cd6\u6838\u9178\u5185\u5207\u9176\u5728\u5207\u5272RNA\u65f6\uff0c\u4f1a\u4ea7\u751f2&#8242;,3&#8242;-\u73af\u78f7\u9178\uff082&#8242;,3&#8242;-cyclic-PO4\uff09\u548c5&#8242;-OH\u672b\u7aef\u3002\u4e3a\u4e86\u4f7f\u8fd9\u4e9b\u672b\u7aef\u80fd\u591f\u88abATP\u4f9d\u8d56\u6027\u8fde\u63a5\u9176\u8bc6\u522b\u548c\u8fde\u63a5\uff0c\u7ec6\u80de\u9700\u8981\u989d\u5916\u7684\u201c\u672b\u7aef\u4fee\u590d\u201d\uff08end-healing\uff09\u9176\uff1a\u4e00\u79cd\u73af\u78f7\u9178\u4e8c\u916f\u9176\u5c062&#8242;,3&#8242;-\u73af\u78f7\u9178\u6c34\u89e3\u4e3a3&#8242;-OH\uff0c\u4e00\u79cd\u591a\u6838\u82f7\u9178\u6fc0\u9176\u5229\u7528ATP\u5c065&#8242;-OH\u78f7\u9178\u5316\u4e3a5&#8242;-PO4 <sup>32<\/sup>\u3002<\/li>\n\n\n\n<li><strong>RTCB\u8fde\u63a5\u9176\u5bb6\u65cf<\/strong>\uff1a\u4e0e\u7ecf\u5178\u8fde\u63a5\u9176\u5f62\u6210\u9c9c\u660e\u5bf9\u6bd4\u7684\u662f\uff0cRTCB\uff08RNA 2&#8242;,3&#8242;-cyclic phosphate and 3&#8242;-phosphate 5&#8242;-hydroxyl ligase\uff09\u662f\u4e00\u4e2a\u72ec\u7279\u7684\u3001\u4f9d\u8d56GTP\u7684\u8fde\u63a5\u9176\u5bb6\u65cf\u3002RTCB\u5728\u7ed3\u6784\u4e0a\u4e0eATP\u4f9d\u8d56\u6027\u8fde\u63a5\u9176\u6beb\u65e0\u540c\u6e90\u6027\uff0c\u5e76\u91c7\u7528\u4e86\u4e00\u79cd\u5b8c\u5168\u4e0d\u540c\u7684\u50ac\u5316\u673a\u5236\u3002\u5176\u6700\u663e\u8457\u7684\u7279\u70b9\u662f\u80fd\u591f\u76f4\u63a5\u8fde\u63a53&#8242;-\u78f7\u9178\uff083&#8242;-PO4\uff09\u548c5&#8242;-OH\u672b\u7aef\uff0c\u4ece\u800c\u7ed5\u8fc7\u4e86\u5bf95&#8217;\u6fc0\u9176\u8fdb\u884c\u672b\u7aef\u4fee\u590d\u7684\u9700\u6c42\u3002\u8fd9\u4e00\u72ec\u7279\u7684\u53cd\u5e94\u901a\u8fc7\u5f62\u6210\u5171\u4ef7\u7684RtcB-(\u7ec4\u6c28\u9170)-GMP\u548cRNA3&#8217;pp5&#8217;G\u4e2d\u95f4\u4f53\u6765\u5b9e\u73b0 <sup>32<\/sup>\u3002<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">3.2 RTCB\u7684\u591a\u91cd\u89d2\u8272<\/h4>\n\n\n\n<p>RTCB\u4e0d\u4ec5\u662f\u4e00\u79cd\u7406\u8bba\u4e0a\u7684\u4fee\u590d\u9176\uff0c\u5b83\u5728\u7ec6\u80de\u5185\u626e\u6f14\u7740\u660e\u786e\u7684\u751f\u7406\u89d2\u8272\uff0c\u5e76\u4e14\u76f4\u63a5\u53c2\u4e0e\u4e86\u5e94\u6fc0\u6761\u4ef6\u4e0b\u7684\u635f\u4f24\u4fee\u590d\u3002<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>\u751f\u7406\u529f\u80fd<\/strong>\uff1a\u5728\u5305\u62ec\u4eba\u7c7b\u5728\u5185\u7684\u540e\u751f\u52a8\u7269\u4e2d\uff0cRTCB\u662f\u7ef4\u6301\u86cb\u767d\u8d28\u5408\u6210\u7a33\u6001\u7684\u5173\u952e\u56e0\u5b50\u3002\u5b83\u4f5c\u4e3atRNA\u8fde\u63a5\u9176\u590d\u5408\u7269\u7684\u6838\u5fc3\u50ac\u5316\u4e9a\u57fa\uff0c\u8d1f\u8d23\u526a\u63a5\u542b\u6709\u5185\u542b\u5b50\u7684tRNA\u524d\u4f53\uff0c\u786e\u4fdd\u6210\u719ftRNA\u7684\u4f9b\u5e94 <sup>32<\/sup>\u3002\u6b64\u5916\uff0c\u5728\u5185\u8d28\u7f51\u5e94\u6fc0\uff08ER stress\uff09\u671f\u95f4\uff0cRTCB\u8fd8\u53c2\u4e0e\u4e86\u672a\u6298\u53e0\u86cb\u767d\u53cd\u5e94\uff08unfolded protein response, UPR\uff09\u7684\u5173\u952e\u8f6c\u5f55\u56e0\u5b50XBP1\u7684mRNA\u526a\u63a5\uff0c\u8fd9\u662f\u4e00\u79cd\u91cd\u8981\u7684\u7ec6\u80de\u5e94\u6fc0\u4fe1\u53f7\u901a\u8def <sup>32<\/sup>\u3002<\/li>\n\n\n\n<li><strong>\u76f4\u63a5\u7684RNA\u635f\u4f24\u4fee\u590d<\/strong>\uff1aRTCB\u5728RNA\u635f\u4f24\u4fee\u590d\u4e2d\u7684\u76f4\u63a5\u8bc1\u636e\u6765\u81ea\u5bf9\u7ec6\u83cc\u7684\u7814\u7a76\u3002\u5728\u7ec6\u83cc\u4e2d\uff08\u5982<em>E. coli<\/em>\uff09\uff0c\u4e0d\u5b58\u5728tRNA\u526a\u63a5\uff0c\u56e0\u6b64RTCB\u7684\u529f\u80fd\u4e00\u5ea6\u6210\u8c1c\u3002\u8fd1\u671f\u7684\u7814\u7a76\u63ed\u793a\uff0c\u5728\u6297\u751f\u7d20\u7b49\u80c1\u8feb\u6761\u4ef6\u4e0b\uff0c\u7ec6\u83cc\u7684\u6838\u7cd6\u4f53RNA\uff08rRNA\uff09\u4f1a\u53d1\u751f\u65ad\u88c2\u3002\u6b64\u65f6\uff0cRtcB\u88ab\u6fc0\u6d3b\uff0c\u8d1f\u8d23\u5c06\u8fd9\u4e9b\u65ad\u88c2\u7684rRNA\u7247\u6bb5\u91cd\u65b0\u8fde\u63a5\u8d77\u6765\uff0c\u6062\u590d\u6838\u7cd6\u4f53\u7684\u529f\u80fd\u3002\u7f3a\u4e4fRtcB\u7684\u7ec6\u83cc\u5728\u89e3\u9664\u80c1\u8feb\u540e\u6062\u590d\u751f\u957f\u5f97\u66f4\u6162\uff0c\u8fd9\u8868\u660e\u4fee\u590d\u548c\u518d\u5229\u7528\u53d7\u635f\u7684rRNA\u662f\u4e00\u79cd\u8282\u7ea6\u80fd\u91cf\u7684\u751f\u5b58\u7b56\u7565\uff0c\u4e3a\u7ec6\u83cc\u63d0\u4f9b\u4e86\u7ade\u4e89\u4f18\u52bf <sup>35<\/sup>\u3002\u8fd9\u662f\u8fc4\u4eca\u4e3a\u6b62\u5173\u4e8e\u9176\u5728\u4f53\u5185\u4e3b\u52a8\u4fee\u590d\u53d7\u635fRNA\u94fe\u7684\u6700\u76f4\u63a5\u3001\u6700\u6709\u529b\u7684\u8bc1\u636e\u4e4b\u4e00\u3002<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">3.3 \u4e34\u5e8a\u76f8\u5173\u6027\uff1aRNA\u52a0\u5de5\u7f3a\u9677\u4e0e\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5<\/h4>\n\n\n\n<p>RNA\u5b8c\u6574\u6027\u7684\u91cd\u8981\u6027\u5728\u4eba\u7c7b\u75be\u75c5\u4e2d\u5f97\u5230\u4e86\u6df1\u523b\u4f53\u73b0\u3002\u5c3d\u7ba1\u76ee\u524d\u7684\u7814\u7a76\u8d44\u6599\u672a\u76f4\u63a5\u5c06RTCB\u57fa\u56e0\u7684\u7a81\u53d8\u4e0e\u7279\u5b9a\u75be\u75c5\u5173\u8054\u8d77\u6765\uff0c\u4f46\u4e0e\u5176\u529f\u80fd\u5bc6\u5207\u76f8\u5173\u7684tRNA\u526a\u63a5\u901a\u8def\u7684\u5176\u4ed6\u7ec4\u5206\u7684\u7f3a\u9677\uff0c\u5df2\u660e\u786e\u4f1a\u5bfc\u81f4\u4e25\u91cd\u7684\u795e\u7ecf\u7cfb\u7edf\u75be\u75c5\u3002\u4f8b\u5982\uff0c\u7f16\u7801tRNA\u526a\u63a5\u5185\u5207\u9176\u7684TSEN\u590d\u5408\u7269\u6216\u6fc0\u9176CLP1\u7684\u57fa\u56e0\u7a81\u53d8\uff0c\u4f1a\u5bfc\u81f4\u8111\u6865\u5c0f\u8111\u53d1\u80b2\u4e0d\u5168\uff08Pontocerebellar Hypoplasia, PCH\uff09\uff0c\u8fd9\u662f\u4e00\u79cd\u4ee5\u4e25\u91cd\u7684\u795e\u7ecf\u53d1\u80b2\u8fdf\u7f13\u548c\u795e\u7ecf\u9000\u884c\u4e3a\u7279\u5f81\u7684\u9057\u4f20\u75c5 <sup>38<\/sup>\u3002\u8fd9\u4e3a\u6211\u4eec\u63d0\u4f9b\u4e86\u4e00\u4e2a\u5f3a\u6709\u529b\u7684\u8303\u4f8b\uff1a\u7cbe\u786e\u7684RNA\u52a0\u5de5\u548c\u4fee\u590d\u5bf9\u4e8e\u7ef4\u6301\u795e\u7ecf\u7cfb\u7edf\u7684\u6b63\u5e38\u53d1\u80b2\u548c\u529f\u80fd\u81f3\u5173\u91cd\u8981\uff0c\u4efb\u4f55\u73af\u8282\u7684\u7f3a\u9677\u90fd\u53ef\u80fd\u5bfc\u81f4\u6bc1\u706d\u6027\u7684\u540e\u679c\u3002<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\" \/>\n\n\n\n<h2 class=\"wp-block-heading\">\u7b2c\u4e8c\u90e8\u5206 \u7cfb\u7edf\u5c42\u9762\u89c6\u89d2\uff1aRNA\u635f\u4f24\u5e94\u7b54\uff08RDR\uff09\u4fe1\u53f7\u7f51\u7edc<\/h2>\n\n\n\n<p>\u5728\u8bc6\u522b\u51fa\u5355\u4e2a\u53c2\u4e0eRNA\u7ef4\u62a4\u7684\u9176\u4e4b\u540e\uff0c\u4e00\u4e2a\u66f4\u6df1\u5c42\u6b21\u7684\u95ee\u9898\u6d6e\u73b0\u51fa\u6765\uff1a\u8fd9\u4e9b\u72ec\u7acb\u7684\u6d3b\u52a8\u662f\u5982\u4f55\u88ab\u6574\u5408\u6210\u4e00\u4e2a\u534f\u8c03\u7684\u3001\u7cfb\u7edf\u5c42\u9762\u7684\u7ec6\u80de\u53cd\u5e94\uff1f\u4e3a\u4e86\u56de\u7b54\u8fd9\u4e2a\u95ee\u9898\uff0c\u6211\u4eec\u53ef\u4ee5\u4ece\u7814\u7a76\u66f4\u4e3a\u6210\u719f\u7684DNA\u635f\u4f24\u5e94\u7b54\uff08DDR\uff09\u4e2d\u6c72\u53d6\u7075\u611f\u3002DDR\u4e0d\u4ec5\u63d0\u4f9b\u4e86\u4e00\u4e2a\u5f3a\u5927\u7684\u6982\u5ff5\u84dd\u56fe\uff0c\u5176\u6838\u5fc3\u7684\u201c\u611f\u5e94\u5668-\u8f6c\u5bfc\u5668-\u6548\u5e94\u5668\u201d\u4fe1\u53f7\u903b\u8f91\u4e5f\u4e3a\u6211\u4eec\u7406\u89e3\u548c\u6784\u5efa\u65b0\u5174\u7684RDR\u7f51\u7edc\u6846\u67b6\u63d0\u4f9b\u4e86\u5b9d\u8d35\u7684\u7ebf\u7d22\u3002<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u7b2c\u56db\u8282 DNA\u635f\u4f24\u5e94\u7b54\uff08DDR\uff09\u4f5c\u4e3a\u6982\u5ff5\u84dd\u56fe<\/h3>\n\n\n\n<h4 class=\"wp-block-heading\">4.1 \u4ece\u5355\u4e2a\u9176\u5230\u534f\u8c03\u7f51\u7edc\uff1a\u5386\u53f2\u7684\u89c6\u89d2<\/h4>\n\n\n\n<p>\u5bf9DNA\u4fee\u590d\u7684\u7814\u7a76\u5386\u7a0b\u672c\u8eab\u5c31\u662f\u4e00\u6b21\u79d1\u5b66\u8ba4\u77e5\u7684\u8303\u5f0f\u8f6c\u53d8\u3002\u65e9\u671f\u7814\u7a76\u96c6\u4e2d\u4e8e\u9274\u5b9a\u5355\u4e2a\u7684\u4fee\u590d\u9176\uff08\u5982DNA\u805a\u5408\u9176\uff09\u548c\u89e3\u6790\u5b64\u7acb\u7684\u4fee\u590d\u901a\u8def\uff08\u5982BER\u3001NER\uff09\u3002\u4e00\u4e2a\u6839\u672c\u6027\u7684\u6982\u5ff5\u98de\u8dc3\uff0c\u7531Leland Hartwell\u7b49\u8bfa\u8d1d\u5c14\u5956\u5f97\u4e3b\u7684\u5de5\u4f5c\u50ac\u751f\uff0c\u5373\u201c\u68c0\u67e5\u70b9\u201d\uff08checkpoint\uff09\u6982\u5ff5\u7684\u63d0\u51fa <sup>41<\/sup>\u3002\u8fd9\u4e00\u601d\u60f3\u5c06\u7814\u7a76\u89c6\u89d2\u4ece\u5355\u7eaf\u7684\u201c\u4fee\u590d\u201d\u63d0\u5347\u5230\u4e86\u201c\u5e94\u7b54\u201d\u3002DDR\u4e0d\u518d\u88ab\u770b\u4f5c\u662f\u4e00\u7cfb\u5217\u72ec\u7acb\u7684\u9176\u4fc3\u53cd\u5e94\uff0c\u800c\u662f\u4e00\u4e2a\u590d\u6742\u7684\u3001\u76f8\u4e92\u8fde\u63a5\u7684\u4fe1\u53f7\u7f51\u7edc\u3002\u8fd9\u4e2a\u7f51\u7edc\u80fd\u591f\u4e3b\u52a8\u611f\u77e5DNA\u635f\u4f24\uff0c\u5e76\u5c06\u635f\u4f24\u4fe1\u53f7\u4e0e\u7ec6\u80de\u5468\u671f\u505c\u6ede\u3001\u4fee\u590d\u86cb\u767d\u62db\u52df\u4e43\u81f3\u7a0b\u5e8f\u6027\u7ec6\u80de\u6b7b\u4ea1\uff08\u51cb\u4ea1\uff09\u7b49\u5173\u952e\u7ec6\u80de\u547d\u8fd0\u51b3\u5b9a\u7d27\u5bc6\u5076\u8054\uff0c\u4ece\u800c\u4f5c\u4e3a\u4e00\u4e2a\u6574\u4f53\u6765\u7ef4\u62a4\u57fa\u56e0\u7ec4\u7684\u5b8c\u6574\u6027 <sup>42<\/sup>\u3002\u8fd9\u6bb5\u4ece\u5b64\u7acb\u9176\u5230\u6574\u5408\u7f51\u7edc\u7684\u79d1\u5b66\u53f2\uff0c\u4e3a\u6211\u4eec\u9884\u6d4b\u548c\u7406\u89e3RNA\u635f\u4f24\u9886\u57df\u5f53\u524d\u7684\u53d1\u5c55\u8f68\u8ff9\u2014\u2014\u5373\u4ece\u9274\u5b9a\u5355\u4e2aRNA\u4fee\u590d\u9176\u5230\u6784\u60f3\u4e00\u4e2a\u7edf\u4e00\u7684RDR\u7f51\u7edc\u2014\u2014\u63d0\u4f9b\u4e86\u5b8c\u7f8e\u7684\u5386\u53f2\u53c2\u7167\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">4.2 \u7ecf\u5178DDR\u7ea7\u8054\u53cd\u5e94\uff1a\u611f\u5e94\u5668\u3001\u8f6c\u5bfc\u5668\u548c\u6548\u5e94\u5668<\/h4>\n\n\n\n<p>\u4e3a\u4e86\u5efa\u7acb\u4e00\u4e2a\u53ef\u4f9b\u6bd4\u8f83\u7684\u6a21\u578b\uff0c\u6211\u4eec\u9996\u5148\u6982\u8ff0DDR\u7684\u6838\u5fc3\u4fe1\u53f7\u903b\u8f91\uff0c\u5b83\u901a\u5e38\u9075\u5faa\u4e00\u4e2a\u4e09\u6bb5\u5f0f\u7ed3\u6784\uff1a<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>\u611f\u5e94\u5668\uff08Sensors\uff09<\/strong>\uff1a\u8fd9\u4e9b\u86cb\u767d\u8d28\u6216\u590d\u5408\u7269\u8d1f\u8d23\u76f4\u63a5\u8bc6\u522bDNA\u635f\u4f24\u7684\u7ed3\u6784\u3002\u5173\u952e\u7684\u4f8b\u5b50\u5305\u62ec\u8bc6\u522bDNA\u53cc\u94fe\u65ad\u88c2\uff08DSBs\uff09\u7684MRN\u590d\u5408\u7269\uff08Mre11-Rad50-NBS1\uff09\uff0c\u4ee5\u53ca\u8bc6\u522b\u5355\u94feDNA\uff08ssDNA\uff09\u533a\u57df\uff08\u901a\u5e38\u5728\u590d\u5236\u505c\u6ede\u65f6\u4ea7\u751f\uff09\u7684\u590d\u5236\u86cb\u767dA\uff08RPA\uff09 <sup>42<\/sup>\u3002<\/li>\n\n\n\n<li><strong>\u8f6c\u5bfc\u5668\uff08Transducers\uff09<\/strong>\uff1a\u8fd9\u4e9b\u901a\u5e38\u662f\u9876\u7aef\u7684\u86cb\u767d\u6fc0\u9176\uff0c\u8d1f\u8d23\u63a5\u6536\u6765\u81ea\u611f\u5e94\u5668\u7684\u4fe1\u53f7\u5e76\u5c06\u5176\u653e\u5927\u3001\u4f20\u9012\u4e0b\u53bb\u3002DDR\u7f51\u7edc\u7684\u6838\u5fc3\u8f6c\u5bfc\u5668\u662f\u4e24\u4e2a\u5c5e\u4e8ePIKK\u6fc0\u9176\u5bb6\u65cf\u7684\u6210\u5458\uff1aATM\uff08ataxia-telangiectasia mutated\uff09\uff0c\u4e3b\u8981\u7531DSBs\u6fc0\u6d3b\uff1b\u4ee5\u53caATR\uff08ATM- and Rad3-Related\uff09\uff0c\u4e3b\u8981\u7531RPA\u5305\u88ab\u7684ssDNA\u6fc0\u6d3b <sup>42<\/sup>\u3002<\/li>\n\n\n\n<li><strong>\u6548\u5e94\u5668\uff08Effectors\uff09<\/strong>\uff1a\u8fd9\u4e9b\u662fATM\u548cATR\u7684\u4e0b\u6e38\u5e95\u7269\uff0c\u8d1f\u8d23\u6267\u884c\u5177\u4f53\u7684\u7ec6\u80de\u53cd\u5e94\u3002\u5b83\u4eec\u5305\u62ec\u6267\u884c\u7ec6\u80de\u5468\u671f\u68c0\u67e5\u70b9\u7684\u6fc0\u9176\uff08\u5982Chk1\u548cChk2\uff09\u548c\u5173\u952e\u7684\u80bf\u7624\u6291\u5236\u56e0\u5b50\uff08\u5982p53\u548cBRCA1\uff09\u3002\u8fd9\u4e9b\u6548\u5e94\u5668\u5171\u540c\u534f\u8c03\u7ec6\u80de\u5468\u671f\u505c\u6ede\u3001DNA\u4fee\u590d\u901a\u8def\u7684\u6fc0\u6d3b\uff0c\u6216\u8005\u5728\u635f\u4f24\u65e0\u6cd5\u4fee\u590d\u65f6\u542f\u52a8\u7ec6\u80de\u51cb\u4ea1\u7a0b\u5e8f <sup>42<\/sup>\u3002<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">\u7b2c\u4e94\u8282 \u63cf\u7ed8RNA\u635f\u4f24\u5e94\u7b54\uff08RDR\uff09\u7f51\u7edc<\/h3>\n\n\n\n<p>\u501f\u9274DDR\u7684\u903b\u8f91\u6846\u67b6\uff0c\u6211\u4eec\u53ef\u4ee5\u5c06\u76ee\u524d\u5df2\u77e5\u7684\u3001\u770b\u4f3c\u96f6\u6563\u7684\u7ec6\u80de\u5bf9RNA\u635f\u4f24\u7684\u53cd\u5e94\uff0c\u6574\u5408\u6210\u4e00\u4e2a\u521d\u5177\u96cf\u5f62\u7684RDR\u7f51\u7edc\u6a21\u578b\u3002\u8fd9\u4e2a\u6a21\u578b\u540c\u6837\u5305\u542b\u611f\u5e94\u3001\u4fe1\u53f7\u8f6c\u5bfc\u548c\u6548\u5e94\u6267\u884c\u7b49\u73af\u8282\uff0c\u4f46\u5176\u7ed3\u6784\u548c\u7ec4\u6210\u4e0eDDR\u65e2\u6709\u76f8\u4f3c\u4e4b\u5904\uff0c\u4e5f\u5b58\u5728\u663e\u8457\u5dee\u5f02\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">5.1 RNA\u635f\u4f24\u7684\u56fe\u666f<\/h4>\n\n\n\n<p>\u4e0e\u6df1\u85cf\u4e8e\u7ec6\u80de\u6838\u5185\u5e76\u53d7\u5230\u4e25\u5bc6\u4fdd\u62a4\u7684DNA\u4e0d\u540c\uff0cRNA\u5728\u7ec6\u80de\u5185\u65e0\u5904\u4e0d\u5728\uff0c\u7ed3\u6784\u4e5f\u66f4\u52a0\u591a\u6837\uff0c\u8fd9\u4f7f\u5176\u9762\u4e34\u7740\u66f4\u5e7f\u6cdb\u7684\u635f\u4f24\u98ce\u9669\u3002\u8fd9\u4e9b\u635f\u4f24\u5305\u62ec\u78b1\u57fa\u7684\u5316\u5b66\u4fee\u9970\uff08\u5982\u70f7\u5316\u3001\u6c27\u5316\u4ea7\u751f8-oxoG\uff09\u3001\u78f7\u9178\u4e8c\u916f\u9aa8\u67b6\u7684\u65ad\u88c2\uff0c\u4ee5\u53ca\u5f62\u6210\u5f02\u5e38\u7684\u4e8c\u7ea7\u6216\u4e09\u7ea7\u7ed3\u6784 <sup>3<\/sup>\u3002\u8fd9\u4e9b\u635f\u4f24\u7684\u540e\u679c\u662f\u4e25\u91cd\u7684\uff0c\u53ef\u80fd\u5bfc\u81f4\u7ffb\u8bd1\u505c\u6ede\u3001\u4ea7\u751f\u5177\u6709\u7ec6\u80de\u6bd2\u6027\u7684\u5f02\u5e38\u86cb\u767d\u8d28\uff0c\u4ee5\u53ca\u7834\u574f\u7cbe\u5bc6\u7684RNA\u8c03\u63a7\u7f51\u7edc <sup>6<\/sup>\u3002\u7279\u522b\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0cRNA\u7684\u6c27\u5316\u635f\u4f24\u6bd4DNA\u66f4\u4e3a\u666e\u904d\uff0c\u5e76\u4e14\u4e0e\u8870\u8001\u548c\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\u7684\u53d1\u751f\u5bc6\u5207\u76f8\u5173\uff0c\u8fd9\u51f8\u663e\u4e86\u7ef4\u6301RNA\u5b8c\u6574\u6027\u7684\u91cd\u8981\u6027 <sup>2<\/sup>\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">5.2 RNA\u635f\u4f24\u7684\u7ec6\u80de\u611f\u5e94\u5668\uff1a\u591a\u7ba1\u9f50\u4e0b\u7684\u7b56\u7565<\/h4>\n\n\n\n<p>DDR\u7684\u4fe1\u53f7\u6d41\u5728\u5f88\u5927\u7a0b\u5ea6\u4e0a\u662f\u96c6\u4e2d\u7684\uff0c\u5373\u4e0d\u540c\u7c7b\u578b\u7684\u635f\u4f24\u6700\u7ec8\u6c47\u96c6\u5230ATM\u548cATR\u8fd9\u4e24\u4e2a\u6838\u5fc3\u6fc0\u9176\u7684\u6fc0\u6d3b\u4e0a\u3002\u76f8\u6bd4\u4e4b\u4e0b\uff0cRDR\u4f3c\u4e4e\u91c7\u7528\u4e86\u4e00\u79cd\u66f4\u4e3a\u5206\u6563\u548c\u7279\u5316\u7684\u611f\u5e94\u7b56\u7565\u3002\u635f\u4f24\u7684\u7c7b\u578b\u3001\u4e25\u91cd\u7a0b\u5ea6\u53ca\u5176\u5728\u7ec6\u80de\u5185\u7684\u4f4d\u7f6e\uff0c\u5171\u540c\u51b3\u5b9a\u4e86\u54ea\u4e00\u4e2a\u611f\u5e94\u7cfb\u7edf\u88ab\u6fc0\u6d3b\uff0c\u4ece\u800c\u542f\u52a8\u4e0d\u540c\u7684\u4e0b\u6e38\u901a\u8def\u3002<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">5.2.1 \u6838\u7cd6\u4f53\u4f5c\u4e3a\u54e8\u5175<\/h5>\n\n\n\n<p>\u4f5c\u4e3a\u86cb\u767d\u8d28\u5408\u6210\u7684\u5de5\u5382\uff0c\u6838\u7cd6\u4f53\u662f\u76d1\u89c6mRNA\u5b8c\u6574\u6027\u7684\u7b2c\u4e00\u7ebf\u3002\u5f53\u7ffb\u8bd1\u673a\u5668\u5728mRNA\u4e0a\u9047\u5230\u635f\u4f24\u6216\u969c\u788d\u65f6\uff0c\u4f1a\u89e6\u53d1\u81f3\u5c11\u4e24\u79cd\u4e0d\u540c\u7684\u5e94\u7b54\u9014\u5f84\uff1a<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>\u6838\u7cd6\u4f53\u6bd2\u6027\u5e94\u6fc0\u53cd\u5e94\uff08Ribotoxic Stress Response, RSR\uff09<\/strong>\uff1a\u5f53\u6838\u7cd6\u4f53\u7531\u4e8emRNA\u4e0a\u7684\u635f\u4f24\u3001\u67d0\u4e9b\u6297\u751f\u7d20\u6216\u7d2b\u5916\u7ebf\u8f90\u5c04\u7b49\u56e0\u7d20\u800c\u53d1\u751f\u505c\u6ede\u6216\u78b0\u649e\u65f6\uff0c\u4e00\u79cd\u540d\u4e3aZAK\u03b1\u7684MAP3K\u6fc0\u9176\u4f1a\u88ab\u6fc0\u6d3b\u3002ZAK\u03b1\u968f\u540e\u542f\u52a8\u4e00\u4e2a\u7531p38\u548cJNK\u4ecb\u5bfc\u7684MAPK\u4fe1\u53f7\u7ea7\u8054\u53cd\u5e94\uff0c\u6700\u7ec8\u5bfc\u81f4\u708e\u75c7\u53cd\u5e94\u548c\u7ec6\u80de\u51cb\u4ea1\u3002RSR\u662f\u4e00\u6761\u4e13\u95e8\u54cd\u5e94\u7ffb\u8bd1\u8fc7\u7a0b\u53d7\u963b\u7684\u4fe1\u53f7\u901a\u8def <sup>55<\/sup>\u3002<\/li>\n\n\n\n<li><strong>\u6838\u7cd6\u4f53\u76f8\u5173\u8d28\u91cf\u63a7\u5236\uff08Ribosome-Associated Quality Control, RQC\uff09<\/strong>\uff1aRQC\u901a\u8def\u5219\u8d1f\u8d23\u5904\u7406\u7ffb\u8bd1\u505c\u6ede\u7684\u201c\u5584\u540e\u201d\u5de5\u4f5c\u3002\u5f53\u6838\u7cd6\u4f53\u53d1\u751f\u78b0\u649e\u65f6\uff0cE3\u6cdb\u7d20\u8fde\u63a5\u9176ZNF598\u7b49\u56e0\u5b50\u4f1a\u8bc6\u522b\u8fd9\u79cd\u5f02\u5e38\u7ed3\u6784\uff0c\u5e76\u5bf9\u6838\u7cd6\u4f53\u86cb\u767d\u548c\u65b0\u751f\u7684\u591a\u80bd\u94fe\u8fdb\u884c\u6cdb\u7d20\u5316\u3002\u8fd9\u6700\u7ec8\u5bfc\u81f4\u65b0\u751f\u80bd\u94fe\u88ab\u86cb\u767d\u9176\u4f53\u964d\u89e3\uff0c\u800c\u505c\u6ede\u7684\u6838\u7cd6\u4f53\u4e9a\u57fa\u88ab\u89e3\u79bb\u548c\u56de\u6536\u3002RQC\u662f\u4e00\u4e2a\u201c\u6e05\u7406\u201d\u901a\u8def\uff0c\u65e8\u5728\u9632\u6b62\u6709\u6bd2\u86cb\u767d\u4ea7\u7269\u7684\u79ef\u7d2f\u548c\u5b9d\u8d35\u6838\u7cd6\u4f53\u8d44\u6e90\u7684\u6d6a\u8d39 <sup>60<\/sup>\u3002<\/li>\n<\/ul>\n\n\n\n<h5 class=\"wp-block-heading\">5.2.2 \u5148\u5929\u514d\u75ab\u611f\u5e94\u5668\uff08RIG-I, MDA5\uff09<\/h5>\n\n\n\n<p>RIG-I\u548cMDA5\u662f\u7ec6\u80de\u8d28\u4e2d\u7ecf\u5178\u7684\u75c5\u6bd2RNA\u611f\u5e94\u5668\uff0c\u5b83\u4eec\u901a\u8fc7\u8bc6\u522b\u975e\u81ea\u8eabRNA\u7684\u7279\u5f81\uff08\u59825&#8242;-\u4e09\u78f7\u9178\u672b\u7aef\u548c\u957f\u7684\u53cc\u94feRNA\u7ed3\u6784\uff09\u6765\u542f\u52a8\u6297\u75c5\u6bd2\u514d\u75ab\u3002\u4e00\u65e6\u88ab\u6fc0\u6d3b\uff0c\u5b83\u4eec\u4f1a\u901a\u8fc7\u63a5\u5934\u86cb\u767dMAVS\u542f\u52a8\u4fe1\u53f7\u7ea7\u8054\uff0c\u6700\u7ec8\u5bfc\u81f4I\u578b\u5e72\u6270\u7d20\uff08IFN\uff09\u7684\u4ea7\u751f\uff0c\u5efa\u7acb\u6297\u75c5\u6bd2\u72b6\u6001 <sup>64<\/sup>\u3002\u81f3\u5173\u91cd\u8981\u7684\u662f\uff0c\u6709\u8bc1\u636e\u8868\u660e\u8fd9\u4e9b\u611f\u5e94\u5668\u5728\u7279\u5b9a\u6761\u4ef6\u4e0b\u4e5f\u53ef\u80fd\u88ab\u5185\u6e90\u6027\u7684\u201c\u81ea\u8eab\u201dRNA\u6fc0\u6d3b\u3002\u8fd9\u6697\u793a\u7740\uff0c\u5b83\u4eec\u53ef\u80fd\u4e5f\u626e\u6f14\u7740\u5e7f\u4e49\u7684\u7ec6\u80deRNA\u635f\u4f24\u611f\u5e94\u5668\u7684\u89d2\u8272\uff0c\u80fd\u591f\u8bc6\u522b\u56e0\u635f\u4f24\u6216\u9519\u8bef\u52a0\u5de5\u800c\u4ea7\u751f\u7684\u5f02\u5e38RNA\u7ed3\u6784\uff0c\u4ece\u800c\u5c06RNA\u635f\u4f24\u4e0e\u5148\u5929\u514d\u75ab\u6fc0\u6d3b\u76f4\u63a5\u8054\u7cfb\u8d77\u6765 <sup>68<\/sup>\u3002<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">5.2.3 R-loop\uff1a\u8fde\u63a5RDR\u4e0e\u7ecf\u5178DDR\u7684\u76f4\u63a5\u6865\u6881<\/h5>\n\n\n\n<p>R-loop\u662f\u4e00\u79cd\u7531\u4e00\u6761RNA\u94fe\u4fb5\u5165DNA\u53cc\u87ba\u65cb\u5f62\u6210\u7684RNA:DNA\u6742\u5408\u94fe\u548c\u4e00\u6761\u88ab\u7f6e\u6362\u7684\u5355\u94feDNA\u7ec4\u6210\u7684\u4e09\u94fe\u6838\u9178\u7ed3\u6784\u3002\u5b83\u4eec\u5728\u8f6c\u5f55\u8fc7\u7a0b\u4e2d\u53ef\u80fd\u81ea\u7136\u5f62\u6210\uff0c\u4f46\u5176\u8fc7\u5ea6\u79ef\u7d2f\u662f\u57fa\u56e0\u7ec4\u4e0d\u7a33\u5b9a\u7684\u4e00\u4e2a\u91cd\u8981\u6765\u6e90\u3002\u4ece\u4fe1\u53f7\u901a\u8def\u7684\u89d2\u5ea6\u770b\uff0cR-loop\u7684\u53d1\u73b0\u63d0\u4f9b\u4e86\u4e00\u6761\u8fde\u63a5RNA\u4e16\u754c\u4e0e\u7ecf\u5178DDR\u7684\u6700\u76f4\u63a5\u3001\u6700\u6df1\u523b\u7684\u7ebd\u5e26\u3002\u79ef\u7d2f\u7684R-loop\u88ab\u7ec6\u80de\u7684\u76d1\u89c6\u7cfb\u7edf\u8bc6\u522b\u4e3a\u4e00\u79cdDNA\u635f\u4f24\u6216\u590d\u5236\u538b\u529b\uff0c\u80fd\u591f\u76f4\u63a5\u6fc0\u6d3bDDR\u7684\u4e24\u5927\u6838\u5fc3\u6fc0\u9176\u2014\u2014ATM\u548cATR\uff0c\u5e76\u542f\u52a8\u5176\u4e0b\u6e38\u7684\u68c0\u67e5\u70b9\u901a\u8def\uff08\u5982ATR-Chk1\u901a\u8def\uff09 <sup>49<\/sup>\u3002<\/p>\n\n\n\n<p>DDR\u4e0eRDR\u5728\u6838\u5fc3\u903b\u8f91\u4e0a\u5b58\u5728\u5171\u6027\uff0c\u4f46\u4e5f\u8868\u73b0\u51fa\u5173\u952e\u5dee\u5f02\u3002\u4e0b\u8868\u5bf9\u8fd9\u4e24\u4e2a\u7cfb\u7edf\u8fdb\u884c\u4e86\u6bd4\u8f83\uff0c\u4ee5\u7a81\u663eRDR\u7f51\u7edc\u7684\u5206\u6563\u5316\u548c\u591a\u6a21\u5757\u7279\u6027\u3002<\/p>\n\n\n\n<p><strong>\u88682\uff1aDNA\u4e0eRNA\u635f\u4f24\u5e94\u7b54\u901a\u8def\u7684\u6bd4\u8f83\u6846\u67b6<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"has-fixed-layout\"><thead><tr><td>\u7279\u5f81<\/td><td>DNA\u635f\u4f24\u5e94\u7b54 (DDR)<\/td><td>RNA\u635f\u4f24\u5e94\u7b54 (RDR)<\/td><\/tr><\/thead><tbody><tr><td><strong>\u4e3b\u8981\u5a01\u80c1<\/strong><\/td><td>\u57fa\u56e0\u7ec4\u4e0d\u7a33\u5b9a\u3001\u7a81\u53d8\u3001\u7ec6\u80de\u6b7b\u4ea1<\/td><td>\u7ffb\u8bd1\u9519\u8bef\u3001\u6bd2\u6027\u86cb\u767d\u4ea7\u751f\u3001\u8c03\u63a7\u5931\u5e38\u3001\u57fa\u56e0\u7ec4\u4e0d\u7a33\u5b9a<\/td><\/tr><tr><td><strong>\u5173\u952e\u635f\u4f24<\/strong><\/td><td>\u53cc\u94fe\u65ad\u88c2 (DSBs), \u5355\u94feDNA (ssDNA), \u78b1\u57fa\u635f\u4f24<\/td><td>\u78b1\u57fa\u4fee\u9970 (m1A, 8-oxoG), \u94fe\u65ad\u88c2, R-loops, \u7ffb\u8bd1\u505c\u6ede<\/td><\/tr><tr><td><strong>\u4e3b\u8981\u611f\u5e94\u5668<\/strong><\/td><td><strong>\u96c6\u4e2d\u5f0f<\/strong>: MRN\u590d\u5408\u7269 (DSBs), RPA (ssDNA)<\/td><td>\u5206\u6563\u5f0f: &#8211; \u6838\u7cd6\u4f53: ZAK\u03b1, ZNF598 (\u7ffb\u8bd1\u505c\u6ede\/\u78b0\u649e) &#8211; \u7ec6\u80de\u8d28: RIG-I, MDA5 (\u5f02\u5e38RNA\u7ed3\u6784) &#8211; \u7ec6\u80de\u6838: R-loop\u8bc6\u522b\u56e0\u5b50 (\u95f4\u63a5\u6fc0\u6d3bATM\/ATR)<\/td><\/tr><tr><td><strong>\u9876\u7aef\u8f6c\u5bfc\u6fc0\u9176<\/strong><\/td><td>ATM (DSBs), ATR (ssDNA\/\u590d\u5236\u538b\u529b)<\/td><td>ZAK\u03b1 (RSR), ATM\/ATR (R-loops), \u5176\u4ed6\u672a\u77e5\u6fc0\u9176<\/td><\/tr><tr><td><strong>\u5173\u952e\u4e0b\u6e38\u901a\u8def<\/strong><\/td><td>Chk1\/Chk2\u68c0\u67e5\u70b9, p53\u51cb\u4ea1, DNA\u4fee\u590d\u901a\u8def (HR, NHEJ, BER)<\/td><td>MAPK (p38\/JNK)\u901a\u8def, RQC\u964d\u89e3\u901a\u8def, I\u578b\u5e72\u6270\u7d20\u901a\u8def, NMD, DDR\u901a\u8def<\/td><\/tr><tr><td><strong>\u6700\u7ec8\u7ec6\u80de\u7ed3\u679c<\/strong><\/td><td>\u7ec6\u80de\u5468\u671f\u505c\u6ede, DNA\u4fee\u590d, \u51cb\u4ea1, \u8870\u8001<\/td><td>\u7ffb\u8bd1\u6291\u5236, \u708e\u75c7, \u514d\u75ab\u5e94\u7b54, \u53d7\u635fRNA\/\u86cb\u767d\u964d\u89e3, \u51cb\u4ea1<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p>DDR\u7684\u9ad8\u5ea6\u96c6\u4e2d\u5316\u54cd\u5e94\u6a21\u5f0f\uff0c\u5373\u4e0d\u540c\u7c7b\u578b\u7684\u635f\u4f24\u4fe1\u53f7\u6700\u7ec8\u6c47\u805a\u4e8eATM\u548cATR\u7684\u6fc0\u6d3b\uff0c\u4f53\u73b0\u4e86\u5176\u7ef4\u62a4\u57fa\u56e0\u7ec4\u8fd9\u4e00\u6838\u5fc3\u84dd\u56fe\u7684\u81f3\u9ad8\u4f18\u5148\u7ea7\u3002\u76f8\u6bd4\u4e4b\u4e0b\uff0cRDR\u7684\u5206\u6563\u5316\u548c\u60c5\u5883\u4f9d\u8d56\u6027\u5219\u53cd\u6620\u4e86\u5176\u5e94\u5bf9\u5a01\u80c1\u7684\u591a\u6837\u6027\u3002\u635f\u4f24\u53d1\u751f\u5728\u7ec6\u80de\u8d28\u4e2d\u7684\u7ffb\u8bd1\u673a\u5668\u4e0a\uff0c\u4f1a\u89e6\u53d1RSR\u548cRQC\u901a\u8def\uff0c\u5176\u4e3b\u8981\u8f93\u51fa\u662f\u8c03\u8282\u7ffb\u8bd1\u548c\u6e05\u9664\u6709\u6bd2\u4ea7\u7269 <sup>56<\/sup>\u3002\u5f02\u5e38\u7684RNA\u7ed3\u6784\uff08\u53ef\u80fd\u662f\u75c5\u6bd2\u6765\u6e90\u6216\u5185\u6e90\u6027\u635f\u4f24\u4ea7\u751f\uff09\u5728\u7ec6\u80de\u8d28\u4e2d\u88abRIG-I\/MDA5\u7b49\u5148\u5929\u514d\u75ab\u611f\u5e94\u5668\u6355\u83b7\uff0c\u5219\u4f1a\u542f\u52a8\u4ee5\u5e72\u6270\u7d20\u4e3a\u6838\u5fc3\u7684\u514d\u75ab\u9632\u5fa1\u53cd\u5e94 <sup>64<\/sup>\u3002\u800c\u5728\u7ec6\u80de\u6838\u5185\uff0c\u7531\u8f6c\u5f55\u5f02\u5e38\u4ea7\u751f\u7684R-loop\u5219\u76f4\u63a5\u52ab\u6301\u4e86\u7ecf\u5178\u7684DDR\u673a\u5668\uff0c\u542f\u52a8ATM\/ATR\u4ecb\u5bfc\u7684\u7ec6\u80de\u5468\u671f\u63a7\u5236\u548cDNA\u4fee\u590d <sup>70<\/sup>\u3002\u8fd9\u4e09\u79cd\u4e0d\u540c\u7684\u635f\u4f24\u8f93\u5165\uff0c\u901a\u8fc7\u4e09\u4e2a\u4e0d\u540c\u7684\u611f\u5e94-\u8f6c\u5bfc\u6a21\u5757\uff0c\u5bfc\u81f4\u4e86\u4e09\u79cd\u622a\u7136\u4e0d\u540c\u7684\u7ec6\u80de\u8f93\u51fa\u3002\u8fd9\u8868\u660eRDR\u662f\u4e00\u4e2a\u9ad8\u5ea6\u667a\u80fd\u5316\u7684\u7f51\u7edc\uff0c\u80fd\u591f\u6839\u636eRNA\u635f\u4f24\u7684\u5177\u4f53\u7c7b\u578b\u548c\u4f4d\u7f6e\uff0c\u7cbe\u786e\u5730\u8c03\u6574\u5176\u54cd\u5e94\u7b56\u7565\uff0c\u4ee5\u5e94\u5bf9\u6700\u76f4\u63a5\u7684\u5a01\u80c1\u3002<\/p>\n\n\n\n<p>\u6700\u521d\uff0c\u672c\u62a5\u544a\u65e8\u5728\u63a2\u8ba8DDR\u80fd\u4e3a\u6211\u4eec\u7406\u89e3RDR\u63d0\u4f9b\u4f55\u79cd\u542f\u793a\u3002\u7136\u800c\uff0cR-loop\u7684\u53d1\u73b0\u5f7b\u5e95\u98a0\u8986\u4e86\u8fd9\u79cd\u5355\u5411\u7684\u501f\u9274\u5173\u7cfb\uff0c\u53cd\u8fc7\u6765\u63ed\u793a\u4e86RDR\u80fd\u4e3a\u6211\u4eec\u7406\u89e3DDR\u63d0\u4f9b\u5168\u65b0\u7684\u89c6\u89d2\u3002\u7ecf\u5178\u6a21\u578b\u8ba4\u4e3a\uff0cDDR\u7684\u6838\u5fc3\u6fc0\u9176ATM\u548cATR\u4e3b\u8981\u76d1\u63a7DNA\u7684\u7269\u7406\u7ed3\u6784\u5b8c\u6574\u6027 <sup>42<\/sup>\u3002\u4f46R-loop\u6fc0\u6d3bATM\/ATR\u7684\u73b0\u8c61\u8868\u660e\uff0c\u8fd9\u4e9b\u6fc0\u9176\u7684\u76d1\u63a7\u8303\u56f4\u8fdc\u4e0d\u6b62\u4e8e\u6b64\uff0c\u5b83\u4eec\u540c\u6837\u5728\u76d1\u89c6\u8f6c\u5f55\u8fc7\u7a0b\u7684\u4fdd\u771f\u5ea6\u4ee5\u53ca\u7531\u6b64\u4ea7\u751f\u7684\u6838\u9178\u4e2d\u95f4\u4f53\u7684\u72b6\u6001\u3002\u5f53RNA\u52a0\u5de5\u8fc7\u7a0b\u51fa\u73b0\u7f3a\u9677\uff08\u4f8b\u5982\uff0c\u526a\u63a5\u56e0\u5b50\u7a81\u53d8\u5bfc\u81f4R-loop\u5f02\u5e38\u79ef\u7d2f\uff09\u65f6\uff0c\u8fd9\u4e2a\u6700\u521d\u6e90\u4e8eRNA\u4e16\u754c\u7684\u95ee\u9898\uff0c\u6700\u7ec8\u4f1a\u4ee5\u4e00\u4e2a\u7ecf\u5178\u7684DDR\u4fe1\u53f7\uff08\u5373ATM\/ATR\u7684\u6fc0\u6d3b\uff09\u5448\u73b0\u51fa\u6765 <sup>49<\/sup>\u3002\u56e0\u6b64\uff0c\u201cRNA\u635f\u4f24\u201d\u4e0d\u518d\u4ec5\u4ec5\u662f\u4e0e\u201cDNA\u635f\u4f24\u201d\u5e73\u884c\u7684\u53e6\u4e00\u4e2a\u95ee\u9898\uff0c\u5b83\u5b8c\u5168\u53ef\u4ee5\u662f\u540e\u8005\u7684\u4e0a\u6e38\u8bf1\u56e0\u3002\u8fd9\u4e00\u53d1\u73b0\u6a21\u7cca\u4e86RDR\u548cDDR\u4e4b\u95f4\u7684\u754c\u9650\uff0c\u6697\u793a\u5b83\u4eec\u53ef\u80fd\u662f\u4e00\u4e2a\u66f4\u4e3a\u5b8f\u5927\u3001\u6574\u5408\u7684\u201c\u6838\u9178\u5b8c\u6574\u6027\u5e94\u7b54\u201d\uff08Nucleic Acid Integrity Response\uff09\u7f51\u7edc\u7684\u7ec4\u6210\u90e8\u5206\u3002<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">\u7b2c\u516d\u8282 \u53d7\u635fRNA\u7684\u547d\u8fd0\uff1a\u4fee\u590d\u4e0e\u964d\u89e3\u7684\u6289\u62e9<\/h3>\n\n\n\n<p>\u5f53\u4e00\u4e2aRNA\u5206\u5b50\u53d7\u635f\u65f6\uff0c\u7ec6\u80de\u9762\u4e34\u4e00\u4e2a\u5173\u952e\u7684\u7b56\u7565\u6289\u62e9\uff1a\u662f\u6295\u5165\u80fd\u91cf\u548c\u8d44\u6e90\u5bf9\u5176\u8fdb\u884c\u4fee\u590d\uff0c\u8fd8\u662f\u5c06\u5176\u964d\u89e3\u5e76\u56de\u6536\u6838\u82f7\u9178\u7528\u4e8e\u4ece\u5934\u5408\u6210\uff1f\u8fd9\u4e2a\u51b3\u5b9a\u5e76\u975e\u4e00\u6210\u4e0d\u53d8\uff0c\u800c\u662f\u53d7\u5230\u751f\u7269\u80fd\u91cf\u5b66\u3001\u635f\u4f24\u7c7b\u578b\u548c\u5206\u5b50\u4e30\u5ea6\u7b49\u591a\u79cd\u56e0\u7d20\u5f71\u54cd\u7684\u52a8\u6001\u5e73\u8861\u8fc7\u7a0b\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">6.1 \u751f\u7269\u80fd\u91cf\u5b66\u4e0e\u7b56\u7565\u9009\u62e9<\/h4>\n\n\n\n<p>\u4ece\u751f\u7269\u80fd\u91cf\u5b66\u7684\u89d2\u5ea6\u770b\uff0c\u4fee\u590d\u4e0e\u964d\u89e3\u7684\u6743\u8861\u662f\u4e00\u79cd\u8d44\u6e90\u4f18\u5316\u3002\u5bf9\u4e8e\u50cfrRNA\u8fd9\u6837\u5728\u7ec6\u80de\u4e2d\u6781\u5176\u4e30\u5bcc\u4e14\u5408\u6210\u8017\u80fd\u5de8\u5927\u7684\u5206\u5b50\uff0c\u4fee\u590d\u663e\u7136\u662f\u66f4\u7ecf\u6d4e\u7684\u7b56\u7565\u3002\u4e00\u4e2a\u6838\u7cd6\u4f53\u5305\u542b\u6570\u5343\u4e2a\u6838\u82f7\u9178\uff0c\u4ece\u5934\u5408\u6210\u4e00\u4e2a\u5b8c\u6574\u6838\u7cd6\u4f53\u9700\u8981\u5de8\u5927\u7684\u80fd\u91cf\u6295\u5165\u3002\u56e0\u6b64\uff0c\u5728\u906d\u53d7\u80c1\u8feb\u5bfc\u81f4\u5927\u91cfrRNA\u65ad\u88c2\u540e\uff0c\u901a\u8fc7RNA\u8fde\u63a5\u9176\uff08\u5982RtcB\uff09\u8fdb\u884c\u4fee\u590d\uff0c\u80fd\u591f\u5feb\u901f\u6062\u590d\u5e9e\u5927\u7684\u6838\u7cd6\u4f53\u5e93\uff0c\u8fd9\u5bf9\u4e8e\u7ec6\u80de\u5728\u80c1\u8feb\u540e\u8fc5\u901f\u6062\u590d\u86cb\u767d\u8d28\u5408\u6210\u80fd\u529b\u81f3\u5173\u91cd\u8981 <sup>35<\/sup>\u3002\u76f8\u53cd\uff0c\u5bf9\u4e8e\u5355\u4e2a\u7684\u3001\u534a\u8870\u671f\u8f83\u77ed\u7684mRNA\u5206\u5b50\uff0c\u964d\u89e3\u5e76\u91cd\u65b0\u8f6c\u5f55\u5408\u6210\u4e00\u4e2a\u65b0\u7684\u62f7\u8d1d\uff0c\u53ef\u80fd\u6bd4\u7ef4\u6301\u4e00\u5957\u590d\u6742\u7684\u3001\u9488\u5bf9\u5404\u79cd\u635f\u4f24\u7684\u4fee\u590d\u7cfb\u7edf\u66f4\u4e3a\u9ad8\u6548 <sup>73<\/sup>\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">6.2 \u590d\u6742\u7684\u76f8\u4e92\u4f5c\u7528\uff1a\u201c\u64e6\u9664\u5668\u201d\u4e0e\u201c\u9605\u8bfb\u5668\u201d\u7684\u535a\u5f08<\/h4>\n\n\n\n<p>mRNA\u4e0am6A\u4fee\u9970\u7684\u547d\u8fd0\u662f\u5c55\u793a\u8fd9\u79cd\u52a8\u6001\u8c03\u63a7\u7684\u7edd\u4f73\u6848\u4f8b\u3002\u4e00\u4e2am6A\u6807\u8bb0\u7684mRNA\u5206\u5b50\uff0c\u5176\u6700\u7ec8\u7684\u547d\u8fd0\u53d6\u51b3\u4e8e\u201c\u64e6\u9664\u5668\u201d\uff08eraser\uff09\u548c\u201c\u9605\u8bfb\u5668\u201d\uff08reader\uff09\u4e4b\u95f4\u7684\u4e00\u573a\u6301\u7eed\u535a\u5f08\u3002<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>\u64e6\u9664\u5668<\/strong>\uff1a\u4ee5ALKBH5\u4e3a\u4ee3\u8868\u7684\u53bb\u7532\u57fa\u5316\u9176\uff0c\u80fd\u591f\u53bb\u9664m6A\u6807\u8bb0\uff0c\u5c06RNA\u6062\u590d\u5230\u672a\u4fee\u9970\u72b6\u6001\u3002\u8fd9\u901a\u5e38\u4f1a\u589e\u52a0mRNA\u7684\u7a33\u5b9a\u6027\uff0c\u6539\u53d8\u5176\u7ffb\u8bd1\u6548\u7387\u6216\u526a\u63a5\u6a21\u5f0f <sup>76<\/sup>\u3002<\/li>\n\n\n\n<li><strong>\u9605\u8bfb\u5668<\/strong>\uff1a\u4ee5YTHDF2\u4e3a\u4ee3\u8868\u7684m6A\u7ed3\u5408\u86cb\u767d\uff0c\u80fd\u591f\u7279\u5f02\u6027\u8bc6\u522b\u5e76\u7ed3\u5408m6A\u4f4d\u70b9\uff0c\u5e76\u62db\u52df\u4e0b\u6e38\u7684\u964d\u89e3\u673a\u5668\uff08\u5982CCR4-NOT\u590d\u5408\u7269\uff09\uff0c\u4ece\u800c\u52a0\u901fmRNA\u7684\u964d\u89e3 <sup>78<\/sup>\u3002<\/li>\n<\/ul>\n\n\n\n<p>\u56e0\u6b64\uff0c\u4e00\u4e2am6A\u4fee\u9970\u7684mRNA\u7684\u534a\u8870\u671f\uff0c\u76f4\u63a5\u7531\u7ec6\u80de\u5185ALKBH5\u548cYTHDF2\u7684\u76f8\u5bf9\u8868\u8fbe\u6c34\u5e73\u3001\u6d3b\u6027\u548c\u4e9a\u7ec6\u80de\u5b9a\u4f4d\u5171\u540c\u51b3\u5b9a\u3002\u5f53ALKBH5\u5360\u4f18\u52bf\u65f6\uff0cmRNA\u8d8b\u5411\u4e8e\u7a33\u5b9a\u5b58\u5728\uff1b\u5f53YTHDF2\u5360\u4f18\u52bf\u65f6\uff0cmRNA\u5219\u88ab\u5feb\u901f\u964d\u89e3\u3002\u8fd9\u79cd\u7ade\u4e89\u6027\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u4f7f\u5f97\u7ec6\u80de\u80fd\u591f\u6839\u636e\u4e0d\u540c\u7684\u751f\u7406\u6216\u75c5\u7406\u4fe1\u53f7\uff0c\u7cbe\u7ec6\u5730\u8c03\u8282\u6210\u5343\u4e0a\u4e07\u6761\u8f6c\u5f55\u672c\u7684\u547d\u8fd0\u3002<\/p>\n\n\n\n<h4 class=\"wp-block-heading\">6.3 \u590d\u6742\u6027\u6848\u4f8b\u7814\u7a76\uff1aALKBH5\/DDIT4-AS1\/UPF1\u8f74<\/h4>\n\n\n\n<p>\u6700\u8fd1\u7684\u4e00\u9879\u7814\u7a76\u63ed\u793a\u4e86\u4e00\u4e2a\u66f4\u4e3a\u590d\u6742\u7684\u8c03\u63a7\u7f51\u7edc\uff0c\u5c06RNA\u53bb\u7532\u57fa\u5316\u3001\u957f\u94fe\u975e\u7f16\u7801RNA\uff08lncRNA\uff09\u548c\u6838\u5fc3\u7684RNA\u8d28\u91cf\u63a7\u5236\u901a\u8def\u2014\u2014\u65e0\u4e49\u4ecb\u5bfc\u7684mRNA\u964d\u89e3\uff08Nonsense-Mediated Decay, NMD\uff09\u2014\u2014\u8054\u7cfb\u5728\u4e00\u8d77\u3002\u5728\u80f0\u817a\u764c\u7ec6\u80de\u4e2d\uff0c\u7814\u7a76\u4eba\u5458\u53d1\u73b0\uff1a<\/p>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li>m6A\u53bb\u7532\u57fa\u5316\u9176ALKBH5\u80fd\u591f\u53bb\u9664lncRNA <em>DDIT4-AS1<\/em>\u4e0a\u7684m6A\u4fee\u9970\uff0c\u4ece\u800c\u4f7f\u5176\u7a33\u5b9a\u6027\u589e\u52a0\uff0c\u8868\u8fbe\u6c34\u5e73\u4e0a\u8c03\u3002<\/li>\n\n\n\n<li>\u7a33\u5b9a\u5316\u7684<em>DDIT4-AS1<\/em>\u968f\u540e\u4e0eNMD\u901a\u8def\u7684\u6838\u5fc3\u56e0\u5b50UPF1\u76f8\u4e92\u4f5c\u7528\u3002<\/li>\n\n\n\n<li>\u8fd9\u79cd\u76f8\u4e92\u4f5c\u7528\u963b\u6b62\u4e86\u78f7\u9178\u9176PP2A\u4e0eUPF1\u7684\u7ed3\u5408\uff0c\u5bfc\u81f4UPF1\u5904\u4e8e\u6301\u7eed\u7684\u8d85\u78f7\u9178\u5316\u72b6\u6001\u3002<\/li>\n\n\n\n<li>\u8d85\u78f7\u9178\u5316\u7684UPF1\u6d3b\u6027\u5f02\u5e38\uff0c\u8fdb\u800c\u5bfc\u81f4\u5176\u53e6\u4e00\u4e2a\u9776\u6807\u2014\u2014\u6291\u764c\u57fa\u56e0<em>DDIT4<\/em>\u7684mRNA\u7a33\u5b9a\u6027\u4e0b\u964d\u800c\u88ab\u964d\u89e3\u3002<\/li>\n\n\n\n<li><em>DDIT4<\/em>\u7684\u4e0b\u8c03\u6700\u7ec8\u89e3\u9664\u4e86\u5bf9mTOR\u4fe1\u53f7\u901a\u8def\u7684\u6291\u5236\uff0c\u4fc3\u8fdb\u4e86\u80f0\u817a\u764c\u7684\u5e72\u6027\u548c\u5316\u7597\u62b5\u6297 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