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Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis
Zhang, WD; Tang, M; Wang, L; Zhou, H; Gao, J; Chen, ZL; Zhao, B; Zheng, P
2023
发表期刊SCIENCE ADVANCES
ISSN2375-2548
卷号9期号:4
摘要Replication stress is a major source of endogenous DNA damage. Despite the identification of numerous pro-teins on replication forks to modulate fork or replication machinery activities, it remains unexplored whether noncoding RNAs can localize on stalled forks and play critical regulatory roles. Here, we identify an uncharac-terized long noncoding RNA NONMMUT028956 (Lnc956 for short) predominantly expressed in mouse embry-onic stem cells. Lnc956 is accumulated on replication forks to prevent fork collapse and preserve genomic stability and is essential for mouse embryogenesis. Mechanistically, it drives assembly of the Lnc956-TRIM28-HSP90B1 complex on stalled forks in an interdependent manner downstream of ataxia telangiectasia and Rad3-related (ATR) signaling. Lnc956-TRIM28-HSP90B1 complex physically associates with minichromosome mainte-nance proteins 2 (MCM2) to minichromosome maintenance proteins 7 (MCM7) hexamer via TRIM28 and directly regulates the CDC45-MCM-GINS (CMG) helicase retention on chromatin. The regulation of Lnc956-TRIM28-HSP90B1 on CMG retention is mediated by HSP90B1's chaperoning function. These findings reveal a player that actively regulates replisome retention to prevent fork collapse.
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/13984
专题科研部门_哺乳动物胚胎发育(郑萍)
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GB/T 7714
Zhang, WD,Tang, M,Wang, L,et al. Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis[J]. SCIENCE ADVANCES,2023,9(4).
APA Zhang, WD.,Tang, M.,Wang, L.,Zhou, H.,Gao, J.,...&Zheng, P.(2023).Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis.SCIENCE ADVANCES,9(4).
MLA Zhang, WD,et al."Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis".SCIENCE ADVANCES 9.4(2023).
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