Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032.
Department of Biological Sciences, Columbia University, New York, NY 10027.
Mol Biol Cell. 2019 Oct 1;30(21):2620-2625. doi: 10.1091/mbc.E19-08-0469. Epub 2019 Sep 4.
During S phase in , chromosomal loci become mobile in response to DNA double-strand breaks both at the break site (local mobility) and throughout the nucleus (global mobility). Increased nuclear exploration is regulated by the recombination machinery and the DNA damage checkpoint and is likely an important aspect of homology search. While mobility in response to DNA damage has been studied extensively in S phase, the response in interphase has not, and the question of whether homologous recombination proceeds to completion in G1 phase remains controversial. Here, we find that global mobility is triggered in G1 phase. As in S phase, global mobility in G1 phase is controlled by the DNA damage checkpoint and the Rad51 recombinase. Interestingly, despite the restriction of Rad52 mediator foci to S phase, Rad51 foci form at high levels in G1 phase. Together, these observations indicate that the recombination and checkpoint machineries promote global mobility in G1 phase, supporting the notion that recombination can occur in interphase diploids.
在 S 期,染色体位点会响应 DNA 双链断裂而发生移动,这种移动不仅发生在断裂部位(局部移动),而且会在整个核内发生(全局移动)。核内的这种大范围探索受到重组机制和 DNA 损伤检查点的调控,很可能是同源搜索的一个重要方面。虽然 DNA 损伤响应中的移动性在 S 期已被广泛研究,但在间期的响应情况尚未得到研究,同源重组是否能在 G1 期完成仍是一个有争议的问题。在这里,我们发现 G1 期会触发全局移动性。与 S 期一样,G1 期的全局移动性受到 DNA 损伤检查点和 Rad51 重组酶的控制。有趣的是,尽管 Rad52 介导线粒体焦点局限于 S 期,但 Rad51 焦点在 G1 期会以高浓度形成。这些观察结果表明,重组和检查点机制促进了 G1 期的全局移动性,支持了在间期二倍体中发生重组的观点。