气候变化领域集成服务门户(CCPortal): ATRX and RECQ5 define distinct homologous recombination subpathways

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DOI	10.1073/pnas.2010370118
	ATRX and RECQ5 define distinct homologous recombination subpathways
	Elbakry A.; Juhász S.; Chan K.C.; Löbrich M.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Homologous recombination (HR) is an important DNA double-strand break (DSB) repair pathway that copies sequence information lost at the break site from an undamaged homologous template. This involves the formation of a recombination structure that is processed to restore the original sequence but also harbors the potential for crossover (CO) formation between the participating molecules. Synthesis-dependent strand annealing (SDSA) is an HR subpathway that prevents CO formation and is thought to predominate in mammalian cells. The chromatin remodeler ATRX promotes an alternative HR subpathway that has the potential to form COs. Here, we show that ATRX-dependent HR outcompetes RECQ5-dependent SDSA for the repair of most two-ended DSBs in human cells and leads to the frequent formation of COs, assessed by measuring sister chromatid exchanges (SCEs). We provide evidence that subpathway choice is dependent on interaction of both ATRX and RECQ5 with proliferating cell nuclear antigen. We also show that the subpathway usage varies among different cancer cell lines and compare it to untransformed cells. We further observe HR intermediates arising as ionizing radiation (IR)-induced ultra-fine bridges only in cells expressing ATRX and lacking MUS81 and GEN1. Consistently, damage-induced MUS81 recruitment is only observed in ATRX-expressing cells. Cells lacking BLM show similar MUS81 recruitment and IR-induced SCE formation as control cells. Collectively, these results suggest that the ATRX pathway involves the formation of HR intermediates whose processing is entirely dependent on MUS81 and GEN1 and independent of BLM. We propose that the predominant ATRX-dependent HR subpathway forms joint molecules distinct from classical Holliday junctions. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Synthesis-dependent strand annealing \| Holliday junctions \| sister chromatid exchanges \| crossovers \| DNA repair synthesis
语种	英语
scopus关键词	cell protein; cycline; GEN1 protein; MUS81 protein; RECQ5 protein; transcriptional regulator ATRX; unclassified drug; Article; cancer cell line; controlled study; crossing over; double strand break repair; gene conversion; Holliday junction; homologous recombination; human; human cell; ionizing radiation; priority journal; protein expression; protein processing; protein protein interaction; sister chromatid exchange; synthesis dependent strand annealing
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180989
作者单位	Radiation Biology and DNA Repair, Technical University of Darmstadt, Darmstadt, 64287, Germany
推荐引用方式 GB/T 7714	Elbakry A.,Juhász S.,Chan K.C.,et al. ATRX and RECQ5 define distinct homologous recombination subpathways[J],2021,118(3).
APA	Elbakry A.,Juhász S.,Chan K.C.,&Löbrich M..(2021).ATRX and RECQ5 define distinct homologous recombination subpathways.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Elbakry A.,et al."ATRX and RECQ5 define distinct homologous recombination subpathways".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).