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黏连蛋白在DNA损伤反应中的新作用

The Emerging Role of Cohesin in the DNA Damage Response.

作者信息

Litwin Ireneusz, Pilarczyk Ewa, Wysocki Robert

机构信息

Institute of Experimental Biology, University of Wroclaw, 50-328 Wroclaw, Poland.

出版信息

Genes (Basel). 2018 Nov 28;9(12):581. doi: 10.3390/genes9120581.

Abstract

Faithful transmission of genetic material is crucial for all organisms since changes in genetic information may result in genomic instability that causes developmental disorders and cancers. Thus, understanding the mechanisms that preserve genome integrity is of fundamental importance. Cohesin is a multiprotein complex whose canonical function is to hold sister chromatids together from S-phase until the onset of anaphase to ensure the equal division of chromosomes. However, recent research points to a crucial function of cohesin in the DNA damage response (DDR). In this review, we summarize recent advances in the understanding of cohesin function in DNA damage signaling and repair. First, we focus on cohesin architecture and molecular mechanisms that govern sister chromatid cohesion. Next, we briefly characterize the main DDR pathways. Finally, we describe mechanisms that determine cohesin accumulation at DNA damage sites and discuss possible roles of cohesin in DDR.

摘要

遗传物质的忠实传递对所有生物体都至关重要,因为遗传信息的改变可能导致基因组不稳定,进而引发发育障碍和癌症。因此,了解维持基因组完整性的机制至关重要。黏连蛋白是一种多蛋白复合体,其典型功能是在S期到后期开始之前将姐妹染色单体结合在一起,以确保染色体的均等分裂。然而,最近的研究表明黏连蛋白在DNA损伤反应(DDR)中具有关键作用。在本综述中,我们总结了在理解黏连蛋白在DNA损伤信号传导和修复中的功能方面的最新进展。首先,我们关注黏连蛋白的结构以及控制姐妹染色单体黏连的分子机制。接下来,我们简要描述主要的DDR途径。最后,我们描述决定黏连蛋白在DNA损伤位点积累的机制,并讨论黏连蛋白在DDR中的可能作用。

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