学科主题基础医学
PTEN regulates RPA1 and protects DNA replication forks
Wang, Guangxi1; Li, Yang1; Wang, Pan1; Liang, Hui1; Cui, Ming1; Zhu, Minglu1; Guo, Limei1; Su, Qian2; Sun, Yujie2; McNutt, Michael A.1; Yin, Yuxin1
关键词Pten Rpa1 Replication Fork Protection Otub1
刊名CELL RESEARCH
2015-11-01
DOI10.1038/cr.2015.115
25期:11页:1189-1204
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology
研究领域[WOS]Cell Biology
关键词[WOS]COLITIS-ASSOCIATED CANCER ; GENOMIC INSTABILITY ; TUMOR SUPPRESSION ; S PHASE ; A RPA ; PATHWAY ; SPECIFICITY ; ACTIVATION ; STABILITY ; MECHANISM
英文摘要

Tumor suppressor PTEN regulates cellular activities and controls genome stability through multiple mechanisms. In this study, we report that PTEN is necessary for the protection of DNA replication forks against replication stress. We show that deletion of PTEN leads to replication fork collapse and chromosomal instability upon fork stalling following nucleotide depletion induced by hydroxyurea. PTEN is physically associated with replication protein A 1 (RPA1) via the RPA1 C-terminal domain. STORM and iPOND reveal that PTEN is localized at replication sites and promotes RPA1 accumulation on replication forks. PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination. RPA1 deletion confers a phenotype like that observed in PTEN knockout cells with stalling of replication forks. Expression of PTEN and RPA1 shows strong correlation in colorectal cancer. Heterozygous disruption of RPA1 promotes tumorigenesis in mice. These results demonstrate that PTEN is essential for DNA replication fork protection. We propose that RPA1 is a target of PTEN function in fork protection and that PTEN maintains genome stability through regulation of DNA replication.

语种英语
WOS记录号WOS:000365049100006
项目编号NSFC 31420103905 ; 81430056 ; 81372491 ; 81321003 ; 2010CB912202
资助机构National Natural Scientific Foundation of China ; China National Major Scientific Program ; Shu Fan Education and Research Foundation ; Lam Chung Nin Foundation for Systems Biomedicine
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50563
专题北京大学基础医学院_北京大学系统生物医学研究所
北京大学基础医学院
作者单位1.Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Basic Med Sci, Inst Syst Biomed,Dept Pathol,Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Peking Univ, Biodynam Opt Imaging Ctr, Beijing 100871, Peoples R China
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GB/T 7714
Wang, Guangxi,Li, Yang,Wang, Pan,et al. PTEN regulates RPA1 and protects DNA replication forks[J]. CELL RESEARCH,2015,25(11):1189-1204.
APA Wang, Guangxi.,Li, Yang.,Wang, Pan.,Liang, Hui.,Cui, Ming.,...&Yin, Yuxin.(2015).PTEN regulates RPA1 and protects DNA replication forks.CELL RESEARCH,25(11),1189-1204.
MLA Wang, Guangxi,et al."PTEN regulates RPA1 and protects DNA replication forks".CELL RESEARCH 25.11(2015):1189-1204.
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