A new class of ultrafine anaphase bridges generated by homologous recombination.

A new class of ultrafine anaphase bridges generated by homologous recombination.
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DOI:
10.1080/15384101.2018.1515555
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发表时间:
2018
期刊:
Cell cycle (Georgetown, Tex.)
影响因子:
--
通讯作者:
West SC
West SC
中科院分区:
其他
文献类型:
--
作者:
Chan YW;West SC

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超细后期桥(UFB)是基因组不稳定性的潜在来源,这是癌症的标志。UFB可以由着丝粒/rDNA基因座处的DNA链烷、由复制应激诱导的晚期复制中间体和端粒处的DNA连接产生。最近,有报道称,DNA通过同源重组产生的相互缠绕产生了一类新的UFB,这类UFB被称为同源重组超细桥(HR-UFB)。HR-UFB在后期用PICH和BLM修饰,随后转化为RPA包被的单链DNA桥。这些姐妹染色单体缠结的断裂导致DNA损伤,可以通过下一个细胞周期中的非同源末端连接来修复,但潜在的后果包括DNA重排、染色体易位和融合。这些HR-UFB的可视化以及它们如何产生的知识提供了分子基础,以解释同源重组的上调或未能解析重组中间体如何导致在某些癌症中观察到的染色体不稳定性的发展。
Ultrafine anaphase bridges (UFBs) are a potential source of genome instability that is a hallmark of cancer. UFBs can arise from DNA catenanes at centromeres/rDNA loci, late replication intermediates induced by replication stress, and DNA linkages at telomeres. Recently, it was reported that DNA intertwinements generated by homologous recombination give rise to a new class of UFBs, which have been termed homologous recombination ultrafine bridges (HR-UFBs). HR-UFBs are decorated with PICH and BLM in anaphase, and are subsequently converted to RPA-coated, single-stranded DNA bridges. Breakage of these sister chromatid entanglements leads to DNA damage that can be repaired by non-homologous end joining in the next cell cycle, but the potential consequences include DNA rearrangements, chromosome translocations and fusions. Visualisation of these HR-UFBs, and knowledge of how they arise, provides a molecular basis to explain how upregulation of homologous recombination or failure to resolve recombination intermediates leads to the development of chromosomal instability observed in certain cancers.
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