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在缺乏Brc1的情况下,Ku可稳定复制叉。

Ku stabilizes replication forks in the absence of Brc1.

作者信息

Sánchez Arancha, Russell Paul

机构信息

Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America.

出版信息

PLoS One. 2015 May 12;10(5):e0126598. doi: 10.1371/journal.pone.0126598. eCollection 2015.

Abstract

DNA replication errors are a major source of genome instability in all organisms. In the fission yeast Schizosaccharomyces pombe, the DNA damage response protein Brc1 binds phospho-histone H2A (γH2A)-marked chromatin during S-phase, but how Brc1 protects genome integrity remains unclear. Here we report that the non-homologous end-joining (NHEJ) protein Ku becomes critical for survival of replication stress in brc1∆ cells. Ku's protective activity in brc1∆ cells does not involve its canonical NHEJ function or its roles in protecting telomeres or shielding DNA ends from Exo1 exonuclease. In brc1∆ pku80∆ cells, nuclear foci of Rad52 homologous recombination (HR) protein increase and Mus81-Eme1 Holliday junction resolvase becomes critical, indicating increased replication fork instability. Ku's localization at a ribosomal DNA replication fork barrier associated with frequent replisome-transcriptosome collisions increases in brc1∆ cells and increased collisions correlate with an enhanced requirement for Brc1. These data indicate that Ku stabilizes replication forks in the absence of Brc1.

摘要

DNA复制错误是所有生物体基因组不稳定的主要来源。在裂殖酵母粟酒裂殖酵母中,DNA损伤反应蛋白Brc1在S期结合磷酸化组蛋白H2A(γH2A)标记的染色质,但Brc1如何保护基因组完整性仍不清楚。在此,我们报道非同源末端连接(NHEJ)蛋白Ku对brc1∆细胞中复制应激的存活至关重要。Ku在brc1∆细胞中的保护活性不涉及其典型的NHEJ功能,也不涉及其在保护端粒或保护DNA末端免受Exo1核酸外切酶作用方面的作用。在brc1∆ pku80∆细胞中,Rad52同源重组(HR)蛋白的核灶增加,Mus81-Eme1 Holliday连接解离酶变得至关重要,表明复制叉不稳定性增加。在brc1∆细胞中,Ku在与频繁的复制体-转录体碰撞相关的核糖体DNA复制叉屏障处的定位增加,并且增加的碰撞与对Brc1的需求增加相关。这些数据表明,在没有Brc1的情况下,Ku稳定复制叉。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f78/4428774/73508f2b0b31/pone.0126598.g001.jpg

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