气候变化领域集成服务门户(CCPortal): CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy

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DOI	10.1073/pnas.2015634118
	CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy
	Giunta S.; Hervé S.; White R.R.; Wilhelm T.; Dumont M.; Scelfo A.; Gamba R.; Wong C.K.; Rancati G.; Smogorzewska A.; Funabiki H.; Fachinetti D.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity to prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of the centromere-specific histone H3 variant CENP-A in safeguarding DNA replication of alpha-satellite repeats to prevent structural aneuploidy. Rapid removal of CENP-A in S phase, but not other cell-cycle stages, caused accumulation of R loops with increased centromeric transcripts, and interfered with replication fork progression. Replication without CENP-A causes recombination at alpha-satellites in an R loop-dependent manner, unfinished replication, and anaphase bridges. In turn, chromosome breakage and translocations arise specifically at centromeric regions. Our findings provide insights into how specialized centromeric chromatin maintains the integrity of transcribed noncoding repetitive DNA during S phase. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CENP-A chromatin; Centromere; Chromosome translocations; DNA replication stress; Genome instability
语种	英语
scopus关键词	centromere protein A; histone H3; anaphase; aneuploidy; Article; cell cycle; cell cycle S phase; chromatin; chromosome breakage; chromosome translocation; controlled study; DNA replication; DNA structure; genetic recombination; genetic transcription; genetic variability; genomic instability; human; human cell; priority journal
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/180381
作者单位	Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, United States; Institut Curie, PSL Research University, CNRS, UMR 144, Paris, F-75005, France; Laboratory of Genome Maintenance, The Rockefeller University, New York, NY 10065, United States; Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, 138648, Singapore
推荐引用方式 GB/T 7714	Giunta S.,Hervé S.,White R.R.,et al. CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy[J],2021,118(10).
APA	Giunta S..,Hervé S..,White R.R..,Wilhelm T..,Dumont M..,...&Fachinetti D..(2021).CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Giunta S.,et al."CENP-A chromatin prevents replication stress at centromeres to avoid structural aneuploidy".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).