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Cancer Cell：FA基因与RAD51-BRCA1/2联合保护DNA复制叉，抑制肿瘤发生

2012-07-16 songbo 生物谷

肿瘤FA基因RAD51BRCA1/2DNA复制叉
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7月10日，Cancer Cell杂志报道，范可尼贫血肿瘤抑制因子可与乳腺癌抑癌基因BRCA1等联合发挥DNA复制叉保护功能。 范可尼贫血（FA）患者中的突变基因与DNA修复基因BRCA1和BRCA2/FANCD1相互作用抑制肿瘤的发生，但目前归因于它们的分子功能不能完全解释其所有的生物学行为。 本研究显示FA基因（包括FANCD2）和BRCA1基因具有某些与DNA修复无关的功能，例如保护停滞

7月10日，Cancer Cell杂志报道，范可尼贫血肿瘤抑制因子可与乳腺癌抑癌基因BRCA1等联合发挥DNA复制叉保护功能。

范可尼贫血（FA）患者中的突变基因与DNA修复基因BRCA1和BRCA2/FANCD1相互作用抑制肿瘤的发生，但目前归因于它们的分子功能不能完全解释其所有的生物学行为。

本研究显示FA基因（包括FANCD2）和BRCA1基因具有某些与DNA修复无关的功能，例如保护停滞的复制叉免遭降解。令人惊讶的是，在FANCD2缺陷细胞中，升高RAD51水平或稳定RAD51纤维可恢复对复制叉的保护。

此外，FANCD2介导的复制叉保护与RAD51功能存在上位效应，这揭示了一个意料之外的，连接FA基因与RAD51和BRCA1/ 2乳腺癌抑制因子的复制叉保护信号通路。

总之，研究结果提示，FA基因，RAD51和BRCA1/2蛋白共同构成一个分子网络，以不依赖于DNA修复的方式，发挥着防止基因组不稳定性和抑制肿瘤发生的功能。

doi:10.1016/j.cell.2011.10.017
PMC:
PMID:

A Distinct Replication Fork Protection Pathway Connects Fanconi Anemia Tumor Suppressors to RAD51-BRCA1/2

Katharina Schlacher, Hong Wu, Maria Jasin

Genes mutated in patients with Fanconi anemia (FA) interact with the DNA repair genes BRCA1 and BRCA2/FANCD1 to suppress tumorigenesis, but the molecular functions ascribed to them cannot fully explain all of their cellular roles. Here, we show a repair-independent requirement for FA genes, including FANCD2, and BRCA1 in protecting stalled replication forks from degradation. Fork protection is surprisingly rescued in FANCD2-deficient cells by elevated RAD51 levels or stabilized RAD51 filaments. Moreover, FANCD2-mediated fork protection is epistatic with RAD51 functions, revealing an unanticipated fork protection pathway that connects FA genes to RAD51 and the BRCA1/2 breast cancer suppressors. Collective results imply a unified molecular mechanism for repair-independent functions of FA, RAD51, and BRCA1/2 proteins in preventing genomic instability and suppressing tumorigenesis.

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    2013-07-01 维他命

    #CEL#

    0

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    2013-02-06 zhaozhouchifen

    #Cell#

    0

  3. 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    2013-06-27 syscxl

    #RAD51#

    0

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objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6094, encryptionId=044a6094fc, topicName=DNA复制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e4137, createdName=meichuangyi, createdTime=Mon Aug 20 08:07:00 CST 2012, time=2012-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423284, encodeId=145d142328488, content=<a href='/topic/show?id=504c368e51' target=_blank style='color:#2F92EE;'>#BRCA1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3687, encryptionId=504c368e51, topicName=BRCA1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3d3767712, createdName=caobinglei8080, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1518969, encodeId=9600151896989, content=<a href='/topic/show?id=da4e368832' target=_blank style='color:#2F92EE;'>#BRCA1/2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3688, encryptionId=da4e368832, topicName=BRCA1/2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ce11226326, createdName=fangcong, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593969, encodeId=4ed1159396908, content=<a href='/topic/show?id=63cc368459' target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=)]
    2013-06-21 xiaoyang_ambs

    #抑制肿瘤#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1958792, encodeId=ed861958e921e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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=Mon Jul 01 00:07:00 CST 2013, time=2013-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868560, encodeId=277b1868560b4, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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encryptionId=4c00549381e, topicName=抑制肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4736501, createdName=xiaoyang_ambs, createdTime=Fri Jun 21 17:07:00 CST 2013, time=2013-06-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780585, encodeId=e29a1e805852f, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Wed Oct 24 09:07:00 CST 2012, time=2012-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2024491, encodeId=d75320244911d, content=<a href='/topic/show?id=044a6094fc' target=_blank style='color:#2F92EE;'>#DNA复制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6094, encryptionId=044a6094fc, topicName=DNA复制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e4137, createdName=meichuangyi, createdTime=Mon Aug 20 08:07:00 CST 2012, time=2012-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423284, encodeId=145d142328488, content=<a href='/topic/show?id=504c368e51' target=_blank style='color:#2F92EE;'>#BRCA1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3687, encryptionId=504c368e51, topicName=BRCA1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3d3767712, createdName=caobinglei8080, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1518969, encodeId=9600151896989, content=<a href='/topic/show?id=da4e368832' target=_blank style='color:#2F92EE;'>#BRCA1/2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3688, encryptionId=da4e368832, topicName=BRCA1/2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ce11226326, createdName=fangcong, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593969, encodeId=4ed1159396908, content=<a href='/topic/show?id=63cc368459' target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=)]
    2012-10-24 12498e67m28暂无昵称

    #cancer cell#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1958792, encodeId=ed861958e921e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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=Mon Jul 01 00:07:00 CST 2013, time=2013-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868560, encodeId=277b1868560b4, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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encryptionId=4c00549381e, topicName=抑制肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4736501, createdName=xiaoyang_ambs, createdTime=Fri Jun 21 17:07:00 CST 2013, time=2013-06-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780585, encodeId=e29a1e805852f, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Wed Oct 24 09:07:00 CST 2012, time=2012-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2024491, encodeId=d75320244911d, content=<a href='/topic/show?id=044a6094fc' target=_blank style='color:#2F92EE;'>#DNA复制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6094, encryptionId=044a6094fc, topicName=DNA复制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e4137, createdName=meichuangyi, createdTime=Mon Aug 20 08:07:00 CST 2012, time=2012-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423284, encodeId=145d142328488, content=<a href='/topic/show?id=504c368e51' target=_blank style='color:#2F92EE;'>#BRCA1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3687, encryptionId=504c368e51, topicName=BRCA1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3d3767712, createdName=caobinglei8080, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1518969, encodeId=9600151896989, content=<a href='/topic/show?id=da4e368832' target=_blank style='color:#2F92EE;'>#BRCA1/2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3688, encryptionId=da4e368832, topicName=BRCA1/2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ce11226326, createdName=fangcong, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593969, encodeId=4ed1159396908, content=<a href='/topic/show?id=63cc368459' target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=)]
    2012-08-20 meichuangyi

    #DNA复制#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1958792, encodeId=ed861958e921e, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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=Mon Jul 01 00:07:00 CST 2013, time=2013-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1868560, encodeId=277b1868560b4, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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encryptionId=4c00549381e, topicName=抑制肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4736501, createdName=xiaoyang_ambs, createdTime=Fri Jun 21 17:07:00 CST 2013, time=2013-06-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780585, encodeId=e29a1e805852f, content=<a href='/topic/show?id=517a4016ac' target=_blank style='color:#2F92EE;'>#cancer cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4016, encryptionId=517a4016ac, topicName=cancer cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Wed Oct 24 09:07:00 CST 2012, time=2012-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2024491, encodeId=d75320244911d, content=<a href='/topic/show?id=044a6094fc' target=_blank style='color:#2F92EE;'>#DNA复制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6094, encryptionId=044a6094fc, topicName=DNA复制)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e4137, createdName=meichuangyi, createdTime=Mon Aug 20 08:07:00 CST 2012, time=2012-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423284, encodeId=145d142328488, content=<a href='/topic/show?id=504c368e51' target=_blank style='color:#2F92EE;'>#BRCA1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3687, encryptionId=504c368e51, topicName=BRCA1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7a3d3767712, createdName=caobinglei8080, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1518969, encodeId=9600151896989, content=<a href='/topic/show?id=da4e368832' target=_blank style='color:#2F92EE;'>#BRCA1/2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3688, encryptionId=da4e368832, topicName=BRCA1/2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ce11226326, createdName=fangcong, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1593969, encodeId=4ed1159396908, content=<a href='/topic/show?id=63cc368459' target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Wed Jul 18 02:07:00 CST 2012, time=2012-07-18, status=1, ipAttribution=)]
    2012-07-18 caobinglei8080

    #BRCA1#

    0

  8. 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    2012-07-18 fangcong

    #BRCA1/2#

    0

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    2012-07-18 智者为医08

    #BRCA#

    0

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