{"id":15327,"date":"2018-11-08T00:00:41","date_gmt":"2018-11-07T16:00:41","guid":{"rendered":"https:\/newsletter.sinica.edu.tw\/?p=15327"},"modified":"2023-03-09T10:19:47","modified_gmt":"2023-03-09T02:19:47","slug":"%e6%b8%b8%e9%9b%a2%e7%ab%af%e7%b2%92dna%e6%b4%bb%e5%8c%96%e5%85%88%e5%a4%a9%e6%80%a7%e5%85%8d%e7%96%ab%e5%8f%8d%e6%87%89%e5%bd%b1%e4%b8%a6%e9%9f%bf%e7%99%8c%e7%97%87%e7%94%9f%e6%88%90","status":"publish","type":"post","link":"https:\/newsletter.sinica.edu.tw\/15327\/","title":{"rendered":"\u3010\u5c08\u6b04\u3011\u6e38\u96e2\u7aef\u7c92DNA\u6d3b\u5316\u5148\u5929\u6027\u514d\u75ab\u53cd\u61c9\u5f71\u4e26\u97ff\u764c\u75c7\u751f\u6210"},"content":{"rendered":"

\u7d30\u80de\u8001\u5316\u4f5c\u7528\u8207\u5148\u5929\u6027\u514d\u75ab\u6a5f\u5236\u7686\u5177\u63a7\u5236\u764c\u75c7\u751f\u6210\u7684\u529f\u80fd\uff0c\u7136\u800c\uff0c\u5169\u8005\u4e4b\u9593\u7684\u4ea4\u4e92\u4f5c\u7528\u5247\u5c1a\u5f85\u91d0\u6e05\u3002\u672c\u7814\u7a76\u767c\u73fe\uff0c\u5927\u91cf\u5b58\u5728\u65bc\u4f7f\u7528\u300c\u66ff\u4ee3\u6027\u5ef6\u9577\u7aef\u7c92\uff08Alternative Lengthening of Telomeres, \u7c21\u7a31ALT\uff09\u6a5f\u5236\u300d \u764c\u7d30\u80de\u4e2d\u7684\u300c\u67d3\u8272\u9ad4\u5916\u7aef\u7c92DNA\u300d\uff08extrachromosomal telomere repeat DNA, \u7c21\u7a31ECTR\uff09\uff0c\u7576\u8a98\u767c\u7d2f\u7a4d\u65bc\u6b63\u5e38\u4eba\u985e\u7d30\u80de\u6642\uff0c\u6703\u6d3b\u5316\u7d30\u80de\u5167\u8ca0\u8cac\u5075\u6e2c\u6e38\u96e2DNA \u7684cGAS-STING\u8def\u5f91\uff0c\u5f15\u767c\u7b2c\u4e00\u578b\u5e72\u64fe\u7d20\u53cd\u61c9\uff0c\u6291\u5236\u7d30\u80de\u751f\u9577\u3002\u7136\u800c\uff0cALT\u764c\u7d30\u80de\u4e2d\uff0ccGAS-STING\u8def\u5f91\u666e\u904d\u4e2d\u65b7\uff0c\u7121\u6cd5\u6b63\u5e38\u555f\u52d5\u5e72\u64fe\u7d20\u53cd\u61c9\uff0c\u56e0\u800c\u8ff4\u907f\u4e86\u5148\u5929\u6027\u514d\u75ab\u6a5f\u5236\uff0c\u9019\u662fALT\u7d30\u80de\u5f97\u4ee5\u767c\u5c55\u6210\u764c\u75c7\u7684\u95dc\u9375\u3002\u6b64\u7814\u7a76\u6210\u679c\u5c07\u53ef\u61c9\u7528\u65bc\u767c\u5c55\u91dd\u5c0dALT\u816b\u7624\u7684\u514d\u75ab\u6cbb\u7642\u3002<\/p>\n

 <\/p>\n

\u4e00\u3001\u7aef\u7c92\u8207\u8001\u5316<\/strong><\/h2>\n

\u7aef\u7c92\uff08Telomere\uff09\u662f\u67d3\u8272\u9ad4\u672b\u7aef\u7684\u4fdd\u8b77\u6027DNA\u7d50\u69cb\uff0c\u75315000-15000\u9e7c\u57fa\u5c0d\u7684TTAGGG\u5e8f\u5217\u7d44\u6210\uff0c\u6b64\u4e00\u7d50\u69cb\u53ef\u9632\u6b62\u67d3\u8272\u9ad4\u672b\u7aef\u91cd\u7d44\u878d\u5408\uff0c\u4e26\u7dad\u8b77\u57fa\u56e0\u9ad4\u7a69\u5b9a\uff0c\u5728\u7f3a\u4e4f\u7aef\u7c92\u7d50\u69cb\u7684\u72c0\u614b\u4e0b\uff0c\u67d3\u8272\u9ad4\u7684\u672b\u7aef\u5c31\u6709\u5982\u65b7\u88c2\u7684DNA\uff0c\u6703\u8a98\u767cDNA\u640d\u5bb3\u53cd\u61c9\uff0c\u555f\u52d5DNA\u4fee\u5fa9\u6a5f\u5236\uff0c\u9020\u6210\u67d3\u8272\u9ad4\u878d\u5408\u3002\u7136\u800c\uff0c\u7aef\u7c92\u7d50\u69cb\u537b\u6709\u4e0d\u7a69\u5b9a\u7684\u7279\u6027\uff0c\u7279\u5225\u662f\u7576\u7aef\u7c92\u8907\u88fd\u6642\uff0c\u56e0\u70baDNA\u8907\u88fd\u6a5f\u5236\u5148\u5929\u9650\u5236\uff0c\u5c0e\u81f4\u7aef\u7c92\u8907\u88fd\u4e0d\u5168\uff0c\u5728\u6bcf\u4e00\u6b21\u7d30\u80de\u5206\u88c2\u5f8c\u90fd\u6703\u8b8a\u77ed\uff0c\u96a8\u8457\u7d30\u80de\u6301\u7e8c\u5206\u88c2\u751f\u9577\uff0c\u6700\u7d42\u9020\u6210\u7aef\u7c92\u904e\u77ed\uff0c\u4fdd\u8b77\u529f\u80fd\u55aa\u5931\uff0c\u7136\u5f8c\u8a98\u767cDNA\u640d\u5bb3\u53cd\u61c9\uff0c\u5f71\u97ff\u7d30\u80de\u6b63\u5e38\u529f\u80fd\uff0c\u9020\u6210\u7d30\u80de\u751f\u9577\u505c\u6eef\u8207\u5f15\u8d77\u7d30\u80de\u8001\u5316; \u5728\u4eba\u9ad4\u5167\uff0c\u751f\u6b96\u7d30\u80de\u5177\u6709\u5145\u8db3\u7684\u7aef\u7c92\u9176\u53ef\u5ef6\u9577\u7aef\u7c92\uff0c\u4f46\u5176\u4ed6\u9ad4\u7d30\u80de\u4ee5\u81f3\u65bc\u6210\u9ad4\u5e79\u7d30\u80de\uff0c\u7686\u56e0\u70ba\u7aef\u7c92\u9176\u7f3a\u4e4f\uff0c\u800c\u4f7f\u5f97\u500b\u9ad4\u7d30\u80de\u7aef\u7c92\u9577\u5ea6\u96a8\u8457\u5e74\u7d00\u589e\u9577\u800c\u9010\u6f38\u8b8a\u77ed\uff0c\u7aef\u7c92\u6e1b\u640d\u56e0\u800c\u6210\u70ba\u500b\u9ad4\u8001\u5316\u7684\u4fc3\u9032\u56e0\u5b50\uff0c\u7aef\u7c92\u751f\u7269\u5b78\u7684\u7814\u7a76\u4e5f\u4e00\u76f4\u4f34\u96a8\u8457\u9577\u751f\u4e0d\u8001\u7684\u8a71\u984c\u3002<\/p>\n

 <\/p>\n

\u4e8c\u3001\u7aef\u7c92\u8207\u764c\u5316<\/strong><\/h2>\n

\u5c31\u764c\u75c7\u751f\u6210\u7684\u89d2\u5ea6\u4f86\u770b\uff0c\u96d6\u7136\u7aef\u7c92\u9577\u5ea6\u9650\u5236\u4e86\u7d30\u80de\u58fd\u547d\uff0c\u4f46\u7aef\u7c92\u8b8a\u77ed\u800c\u5f15\u8d77\u7d30\u80de\u8207\u500b\u9ad4\u8001\u5316\u7684\u73fe\u8c61\uff0c\u537b\u662f\u91cd\u8981\u7684\u764c\u75c7\u6291\u5236\u6a5f\u5236\u3002\u764c\u75c7\u7684\u751f\u6210\u4ef0\u8cf4\u764c\u7d30\u80de\u767c\u5c55\u51fa\u7aef\u7c92\u7dad\u8b77\u6a5f\u5236\uff0c\u4ee5\u7dad\u6301\u5176\u7d30\u80de\u6c38\u751f\uff0c\u764c\u7d30\u80de\u4e3b\u8981\u662f\u900f\u904e\u8a98\u767c\u7aef\u7c92\u9176\u5927\u91cf\u8868\u9054\u4f86\u5ef6\u9577\u7aef\u7c92\uff0c\u800c\u7f3a\u4e4f\u7aef\u7c92\u9176\u7684\u764c\u7d30\u80de\u5247\u662f\u5229\u7528\u300c\u66ff\u4ee3\u6027\u5ef6\u9577\u7aef\u7c92\uff08Alternative Lengthening of Telomeres, \u7c21\u7a31ALT\uff09\u300d\u6a5f\u5236\u4f86\u7dad\u8b77\u7aef\u7c92\u7d50\u69cb\uff0c\u6b64\u4e00\u6a5f\u5236\u5229\u7528DNA\u540c\u6e90\u91cd\u7d44\uff0c\u4ee5DNA\u4fee\u5fa9\u5408\u6210\u7684\u65b9\u5f0f\u5ef6\u9577\u7aef\u7c92\uff0c\u7d04\u670910-15%\u7684\u816b\u7624\u662f\u5229\u7528 ALT\u6a5f\u5236\u4f86\u7dad\u8b77\u5176\u7aef\u7c92\u9577\u5ea6\uff0c\u7279\u5225\u662f\u5728\u5305\u62ec\u5152\u7ae5\u8166\u7624(Pediatric glioblastoma)\u3001\u8edf\u7d44\u7e54\u7624 (Soft tissue sarcoma)\u53ca\u9aa8\u764c(Osteosarcoma)\u7684\u764c\u7d30\u80de\u4e2d\uff0cALT\u662f\u5176\u4e3b\u8981\u7684\u7aef\u7c92\u7dad\u8b77\u6a5f\u5236\uff0cALT\u816b\u7624\u7d30\u80de\u4e2d\u5b58\u5728\u5927\u91cf\u67d3\u8272\u9ad4\u5916\u7aef\u7c92(Extrachromosomal Telomere Repeats, ECTR) DNA\uff0c\u96d6\u7136\u76ee\u524dECTR \u5df2\u88ab\u61c9\u7528\u4f5c\u70ba\u6aa2\u6e2c ALT \u816b\u7624\u7684\u7368\u7279\u751f\u7269\u6a19\u8a18\uff0c\u4f46\u5728\u5df2\u767c\u8868\u7684\u6587\u737b\u4e2d\uff0c\u95dc\u65bc\u6e38\u96e2\u5728\u7d30\u80de\u5167\u7684ECTR DNA\u5982\u4f55\u5f71\u97ffALT \u764c\u7d30\u80de\u767c\u5c55\u8207\u751f\u6210\u9084\u6709\u5f85\u91d0\u6e05\u3002<\/p>\n

 <\/p>\n

\u4e09\u3001ECTR\u8a98\u767c\u7d30\u80de\u53cd\u61c9<\/strong><\/h2>\n

\u70ba\u4e86\u7814\u7a76\u7d30\u80de\u5c0d\u65bcECTR\u7d2f\u7a4d\u7684\u53cd\u61c9\uff0c\u6211\u5011\u7814\u7a76\u5718\u968a\u5efa\u7acb\u4e00\u5957\u4f7f\u7d30\u80de\u7522\u751f ECTR\u7684\u8a98\u5c0e\u7cfb\u7d71\uff0c\u53ef\u5728\u6b63\u5e38\u4eba\u985e\u7e96\u7dad\u6bcd\u7d30\u80de\u4e2d\u8a98\u767c\u5927\u91cfECTR\u7522\u751f\uff0c\u6709\u8da3\u7684\u662f\uff0c\u6211\u5011\u767c\u73fe\u6e90\u81ea\u65bc\u7d30\u80de\u6838\u7aef\u7c92\u7684ECTR\u6703\u8f49\u79fb\u81f3\u7d30\u80de\u8cea\u4e2d\uff0c\u4e26\u88abcGAS\u611f\u77e5\u86cb\u767d\u5075\u6e2c (\u57161A)\uff0c\u9032\u800c\u900f\u904ecGAS-STING\u8a0a\u606f\u8def\u5f91\u4f86\u6d3b\u5316IRF3\u8f49\u9304\u56e0\u5b50\uff0c\u8a98\u767c\u7b2c\u4e00\u578b\u5e72\u64fe\u7d20\u8868\u9054\uff0c\u555f\u52d5\u7b2c\u4e00\u578b\u5e72\u64fe\u7d20\u53cd\u61c9\uff0c\u4e26\u9020\u6210\u7d30\u80de\u751f\u9577\u505c\u6eef (\u57161B)\uff0c\u6b64\u5e72\u64fe\u7d20\u53cd\u61c9\u70ba\u5148\u5929\u514d\u75ab\u7cfb\u7d71\u7684\u4e00\u90e8\u5206\uff0c\u4e3b\u8981\u662f\u7528\u4f86\u5075\u6e2c\u75c5\u6bd2\u8207\u7d30\u83cc\u7684\u611f\u67d3\uff0c\u900f\u904e\u5075\u6e2c\u5fae\u751f\u7269DNA\uff0c\u9020\u6210cGAS-STING\u8def\u5f91\u7684\u6d3b\u5316\uff0c\u8a98\u767c\u4e00\u7d1a\u5e72\u64fe\u7d20\u53ca\u767c\u708e\u7d30\u80de\u7d20\u7684\u751f\u6210\u8207\u91cb\u653e\uff0c\u9054\u5230\u6291\u5236\u5fae\u751f\u7269\u611f\u67d3\u7684\u76ee\u7684\uff0c\u800c\u6211\u5011\u7684\u7814\u7a76\u9996\u6b21\u6307\u51fa\uff0cECTR\u5c31\u50cf\u662f\u7d30\u80de\u5167\u6e90\u6027\u7684\u523a\u6fc0\u7269\uff0c\u56e0\u70ba\u7531\u7d30\u80de\u6838\u8f49\u79fb\u5230\u4e0d\u61c9\u8a72\u5b58\u5728\u7684\u7d30\u80de\u8cea\u4e2d\uff0c\u4e5f\u6703\u50cf\u75c5\u539f\u9ad4\u4e00\u6a23\u6d3b\u5316cGAS-STING\u8def\u5f91\uff0c\u8a98\u767c\u5148\u5929\u514d\u75ab\u53cd\u61c9\u3002<\/p>\n

 <\/p>\n

\"\"

\u3010A\u3011ECTR\u65bc\u7e96\u7dad\u6bcd\u7d30\u80de\u5167\uff0c\u5728\u7d30\u80de\u8cea\u4e2d\u88abcGAS\u86cb\u767d\u8fa8\u8a8d\uff08\u767d\u8272\u6846\uff09\uff0c\u7aef\u7c92DNA\u7d93\u7531\u7aef\u7c92\u539f\u4f4d\u96dc\u4ea4\u6cd5\u5075\u6e2c \uff08Telomere\uff0c\u7d05\u8272\uff09\uff0ccGAS\u86cb\u767d\u7531\u514d\u75ab\u67d3\u8272\u6a19\u5b9a\uff08\u7da0\u8272\uff09\uff0c\u7d30\u80deDNA\uff08\u85cd\u8272\uff09\u4f4d\u65bc\u7d30\u80de\u6838\u4e2d\u3002
\u3010B\u3011ECTR\u900f\u904ecGAS\u6d3b\u5316DNA\u611f\u77e5\u8def\u5f91\uff0c\u6291\u5236\u7d30\u80de\u751f\u9577\uff0c\u7576cGAS\u8868\u9054\u53d7\u5230\u6291\u5236(-cGAS), \u7d30\u80de\u751f\u9577\u4e0d\u53d7ECTR\u5f71\u97ff\u3002<\/p><\/div>\n

 <\/p>\n

\u56db\u3001ALT\u764c\u7d30\u80de\u7684DNA\u611f\u77e5\u529f\u80fd\u55aa\u5931<\/strong><\/h2>\n

\u7136\u800c\uff0c\u5728ALT\u764c\u7d30\u80de\u682a\u4e2d\uff0ccGAS-STING \u8def\u5f91\u537b\u7121\u6cd5\u88ab\u6d3b\u5316\uff0c\u56e0\u70baSTING\u86cb\u767d\u7684\u8868\u73fe\u5ee3\u6cdb\u53d7\u5230\u6291\u5236 (\u57162B)\uff0c\u9020\u6210 cGAS-STING\u8def\u5f91\u4e2d\u65b7\uff0c\u56e0\u6b64\u96d6\u7136\u5927\u91cfECTR\u5b58\u5728\u65bcALT\u764c\u7d30\u80de\u4e2d (\u57162A)\uff0c\u4e14\u7d30\u80de\u8cea\u4e2d\u4e5f\u53ef\u5075\u6e2c\u5230ECTR\uff0c\u4f46ECTR \u7684\u7d2f\u7a4d\uff0c\u4ea6\u6216\u662f\u5916\u6e90\u6027 DNA \u523a\u6fc0\uff0c\u90fd\u7121\u6cd5\u555f\u52d5\u5e72\u64fe\u7d20\u53cd\u61c9\uff0c\u764c\u7d30\u80de\u4e5f\u6703\u4e0d\u65b7\u7684\u589e\u751f \u3002 \u5f9e\u816b\u7624\u767c\u5c55\u7684\u89d2\u5ea6\u4f86\u770b\uff0c cGAS-STING \u8def\u5f91\u7684\u7f3a\u5931\uff0c\u6709\u5229\u65bc\u5bcc\u542b ECTR\u7684ALT\u764c\u7d30\u80de\u8ff4\u907f\u7b2c\u4e00\u7d1a\u5e72\u64fe\u7d20\u53cd\u61c9\u5f15\u767c\u7684\u751f\u9577\u6291\u5236\uff0c\u6b64\u70baALT\u764c\u7d30\u80de\u767c\u5c55\u7684\u5fc5\u8981\u689d\u4ef6\u3002<\/p>\n

\"\"

\u57162.
\u3010A\u3011ALT\u7d30\u80de (WI38-VA13, U2OS, Saos2) \u5b58\u5728\u5167\u6e90\u6027ECTR (\u7bad\u982d)\uff0c\u4f46\u6b63\u5e38\u80ba\u7e96\u7dad\u6bcd\u7d30\u80deWI38 \u5247\u7121ECTR\u3002
\u3010B\u3011STING\u8868\u9054\u65bcBJ\u7e96\u7dad\u6bcd\u7d30\u80de\uff0c\u5177\u7aef\u7c92\u9176\u764c\u4e4b\u7d30\u80deMG63\uff0c\u4f46STING\u8868\u9054\u5728ALT\u764c\u7d30\u80deG292, U2OS\u548cSaos2\u4e2d\u53d7\u5230\u6291\u5236\u3002
C, ECTR \u6d3b\u5316cGAS-STING\u8def\u5f91\uff0c\u8a98\u767c\u7b2c\u4e00\u578b\u5e72\u64fe\u7d20\u53cd\u61c9\uff0c\u6291\u5236\u7d30\u80de\u751f\u9577\uff0c\u4f46ALT\u764c\u7d30\u80de\u55aa\u5931\u6b64\u5206\u5b50\u6a5f\u5236\uff0c\u56e0\u800c\u53ef\u6301\u7e8c\u751f\u9577\uff0c\u4e26\u53ef\u80fd\u56e0\u800c\u8eb2\u907f\u514d\u75ab\u5075\u6e2c\u3002<\/p><\/div>\n

 <\/p>\n

\u4e94\u3001\u4ee5\u6bd2\u653b\u6bd2\uff0c\u4ee5\u5937\u5236\u5937\u7684\u764c\u75c7\u6cbb\u7642\u65b0\u65b9\u5411<\/strong><\/h2>\n

\u5728\u9019\u7814\u7a76\u4e2d\uff0c\u6211\u5011\u767c\u73feECTR\u85c9\u7531cGAS-STING\u8a98\u767c\u7b2c\u4e00\u578b\u5e72\u64fe\u7d20\u53cd\u61c9\uff0c\u4e26\u6291\u5236\u4eba\u985e\u7e96\u7dad\u6bcd\u7d30\u80de\u751f\u9577\uff0c\u76f8\u540c\u7684\u7d30\u80de\u53cd\u61c9\u4e5f\u767c\u751f\u65bc\u75c5\u539f\u83cc\u611f\u67d3\uff0c\u53d7\u5230\u5fae\u751f\u7269DNA\u8a98\u767c\uff0c\u9019\u662f\u7528\u4f86\u62b5\u79a6\u5916\u4f86\u611f\u67d3\u7684\u5148\u5929\u6027\u514d\u75ab\u53cd\u61c9\uff0c \u91cd\u8981\u7684\u662f\uff0cALT\u764c\u7d30\u80de\u6709\u91cd\u5927\u7684cGAS-STING\u8def\u5f91\u7f3a\u9677\uff0c\u9019\u6216\u8a31\u53ef\u4ee5\u5e6b\u52a9ALT\u764c\u7d30\u80de\u751f\u9577\uff0c\u4e26\u4fc3\u9032\u816b\u7624\u514d\u75ab\u9003\u812b (\u57162C)\uff0c\u4f46ALT\u816b\u7624\u7d30\u80de\u537b\u4e5f\u56e0\u6b64\u7f3a\u4e4f\u53ef\u7528\u4f86\u5c0d\u6297\u75c5\u6bd2\u611f\u67d3\u7684\u5148\u5929\u6027\u514d\u75ab\u53cd\u61c9\uff0c\u56e0\u6b64\u6211\u5011\u9810\u671f\uff0c\u7f8e\u570bFDA\u8fd1\u671f\u6838\u53ef\uff0c\u5229\u7528\u91cd\u7d44\u76b0\u75b9\u75c5\u6bd2 HSV\u4f5c\u70ba\u6eb6\u7624\u75c5\u6bd2(Oncolytic viruses )\u7684\u514d\u75ab\u7642\u6cd5\uff0c\u61c9\u53ef\u61c9\u7528\u65bcALT\u764c\u75c7\u7684\u6cbb\u7642\uff0c\u53e6\u4e00\u65b9\u9762\uff0c\u56e0\u70baECTR\u4e5f\u53ef\u5728\u7279\u5225\u7684\u751f\u7406\u72c0\u614b\u4e0b\u7522\u751f\u65bc\u4e00\u822c\u9ad4\u7d30\u80de\u4e2d\uff0c\u56e0\u6b64\u900f\u904e\u7814\u7a76ECTR\uff0c\u6216\u8a31\u6709\u66f4\u591a\u8207\u7aef\u7c92\u76f8\u95dc\u7684\u7d30\u80de\u529f\u80fd\uff0c\u7b49\u5f85\u6211\u5011\u53bb\u767c\u73fe\u3002<\/p>\n

 <\/p>\n

Publication<\/p>\n

\u201cExtrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway\u201d, Nature Structural & Molecular Biology<\/em> 24:12 (2017):DOI:10.1038\/nsmb.3498<\/p>\n","protected":false},"excerpt":{"rendered":"

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