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Cell：新型蛋白酶可有效拆散DNA-蛋白质间的交联 助力癌症靶向疗法的开发

2014-07-09 佚名 不详

蛋白酶蛋白质
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DNA-携带遗传信息的载体，其时刻被外源性和内源性的损伤所威胁；DNA-蛋白质间的交叉连接是非常特殊的DNA损害，截至目前为止没有人清楚特殊靶向DNA-蛋白质交联的修复机制。近日，刊登在国际杂志Cell上的一篇研究论文中，来自马克斯普朗克生物研究所的科学家们通过研究发现了一种特殊的蛋白酶，其可以有效切掉DNA-蛋白质交联结构上的蛋白质组分，从而使得有机体可以在DNA-蛋白交联的状态下进行遗传信

DNA-携带遗传信息的载体，其时刻被外源性和内源性的损伤所威胁；DNA-蛋白质间的交叉连接是非常特殊的DNA损害，截至目前为止没有人清楚特殊靶向DNA-蛋白质交联的修复机制。近日，刊登在国际杂志Cell上的一篇研究论文中，来自马克斯普朗克生物研究所的科学家们通过研究发现了一种特殊的蛋白酶，其可以有效切掉DNA-蛋白质交联结构上的蛋白质组分，从而使得有机体可以在DNA-蛋白交联的状态下进行遗传信息的复制，这对于理解机体基因组的完整性以及癌症的发展非常重要。

多种类型的损伤都会对每个细胞中的DNA产生严重的影响，活性化合物，比如甲醛都可以引发DNA发生特殊类型的损伤，这种损伤是细胞反应的副产品，其容易促使蛋白质和DNA之间发生交叉连接（交联）；更为重要的是，这些所谓的DNA-蛋白质之间的交联也会由抗癌药物而引发，交联反应可以干扰DNA正常的复制，对细胞具有毒性影响。

细胞需要展开及分裂DNA来进行双螺旋的复制从而产生自身的遗传物质，而DNA-蛋白质之间的交联作用(DPCs)可以通过阻断解旋酶复制解旋酶来阻断DNA的复制过程，从而抑制细胞的分裂。研究者Stefan Jentsch表示，如今我们鉴别出了一种名为Wss1的蛋白酶，其是一种安全防护因子，可以“砍下”DNA-蛋白质交联结构中的蛋白质组分，从而使得细胞可以进行基因组DNA的复制。

研究者表示，缺少Wss1蛋白酶的细胞对于甲醛尤其敏感，其易受DNA-蛋白质之间交联作用的影响，容易引起基因组不稳定性的产生；值得注意的是，蛋白酶Wss1可以在DNA存在的情况下清除蛋白质，这就表明Wss1可以为基因组有效地移除交联反应从而保证基因组的稳定性。

由于DNA的损伤修复对于预防癌症非常必要，而且理解隐藏在DNA损伤修复下的细胞机制也显得至关重要；DNA-蛋白质之间的交联作用路径的鉴别对于细胞进行快速分裂很重要，因此这项研究中Wss1蛋白酶的鉴别对于未来科学家们开发新型靶向药物来治疗癌症提供了一定的希望和研究思路。

原始出处

Stingele J1, Schwarz MS1, Bloemeke N1, Wolf PG1, Jentsch S2.A DNA-Dependent Protease Involved in DNA-Protein Crosslink Repair.Cell. 2014 Jul 3.

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    2014-12-24 柳叶一刀

    #白质#

    0

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    2015-06-19 医者仁心

    #蛋白酶#

    0

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    2015-02-20 zhaozhouchifen

    #Cell#

    0

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    2014-09-27 维他命

    #CEL#

    0

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    2014-07-11 cmj8wellington

    #蛋白质#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1765527, encodeId=d1701e65527d8, content=<a href='/topic/show?id=252ae1803a3' target=_blank style='color:#2F92EE;'>#白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71803, encryptionId=252ae1803a3, topicName=白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Wed Dec 24 01:10:00 CST 2014, time=2014-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1945132, encodeId=8a1c19451325c, content=<a href='/topic/show?id=249488e60fe' target=_blank style='color:#2F92EE;'>#蛋白酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88760, encryptionId=249488e60fe, topicName=蛋白酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Fri Jun 19 00:10:00 CST 2015, time=2015-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868854, encodeId=576a186885499, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Fri Feb 20 13:10:00 CST 2015, time=2015-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959098, encodeId=c50c195909861, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Sep 27 22:10:00 CST 2014, time=2014-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1296890, encodeId=4c29129689079, content=<a href='/topic/show?id=158288e017c' target=_blank style='color:#2F92EE;'>#蛋白质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88701, encryptionId=158288e017c, topicName=蛋白质)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Fri Jul 11 00:10:00 CST 2014, time=2014-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1378525, encodeId=b33513e8525e4, content=<a href='/topic/show?id=2cf09992871' target=_blank style='color:#2F92EE;'>#靶向疗法#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99928, encryptionId=2cf09992871, topicName=靶向疗法)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b676418, createdName=yanghan, createdTime=Fri Jul 11 00:10:00 CST 2014, time=2014-07-11, status=1, ipAttribution=)]
    2014-07-11 yanghan

    #靶向疗法#

    0