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Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis

文献类型：期刊论文

作者Zhang, Weidao2,3; Tang, Min2,3,4; Wang, Lin2,3; Zhou, Hu5,6; Gao, Jing5,6; Chen, Zhongliang1,7; Zhao, Bo3; Zheng, Ping2,3,8
刊名SCIENCE ADVANCES
出版日期2023-01-27
卷号9期号:4页码:19
ISSN号2375-2548
DOI10.1126/sciadv.adf6277
通讯作者Zhao, Bo(zhaobo@mail.kiz.ac.cn) ; Zheng, Ping(zhengp@mail.kiz.ac.cn)
英文摘要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.
WOS关键词DNA-DAMAGE RESPONSE ; DYNAMICS ; COLLAPSE ; REPAIR ; HSP90 ; MECHANISMS ; STRESS ; IMPACT ; CANCER ; FILIA
资助项目National Natural Science Foundation of China[31930027] ; National Natural Science Foundation of China[32000422] ; National Key Research and Developmental Program of China[2021YFA1102002] ; Yunnan Fundamental Research Projects[202001AT070140] ; Yunnan Fundamental Research Projects[2019FB049] ; exchange program of State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences[GREKF21-14]
WOS研究方向Science & Technology - Other Topics
语种英语
出版者AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号WOS:000981712400010
源URL[http://119.78.100.183/handle/2S10ELR8/306535]  
专题中国科学院上海药物研究所
通讯作者Zhao, Bo; Zheng, Ping
作者单位1.Guizhou Med Univ, Natl Joint Local Engn Lab Cell Engn & Biomed Tech, Guiyang, Peoples R China
2.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China
3.Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech Prov, Kunming 650223, Yunnan, Peoples R China
4.Univ Chinese Acad Sci, Beijing 101408, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
7.Guizhou Med Univ, Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, Guiyang, Peoples R China
8.Chinese Acad Sci, Kunming Inst Zool, CHUK Joint Lab Bioresources & Mol Res Common Dis, KIZ, Kunming 650223, Yunnan, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Weidao,Tang, Min,Wang, Lin,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):19.
APA Zhang, Weidao.,Tang, Min.,Wang, Lin.,Zhou, Hu.,Gao, Jing.,...&Zheng, Ping.(2023).Lnc956-TRIM28-HSP90B1 complex on replication forks promotes CMG helicase retention to ensure stem cell genomic stability and embryogenesis.SCIENCE ADVANCES,9(4),19.
MLA Zhang, Weidao,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):19.

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来源：上海药物研究所

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