期刊
MOLECULAR CELL
卷 64, 期 6, 页码 1127-1134出版社
CELL PRESS
DOI: 10.1016/j.molcel.2016.10.038
关键词
-
资金
- Swiss National Science Foundation [SNF 160322, CRSI33_130016]
- European Commission (ERC ONIDDAC)
- Novo Nordisk Foundation [NNF 14CC0001]
- Danish Cancer Society [R72-A4436]
- Greek GSRT Program [Aristeia II-3020]
- EMBO long-term postdoctoral fellowship
- Novo Nordisk Foundation Center for Protein Research [PI Jiri Lukas] Funding Source: researchfish
- The Danish Cancer Society [R72-A4436] Funding Source: researchfish
- Swiss National Science Foundation (SNF) [CRSI33_130016] Funding Source: Swiss National Science Foundation (SNF)
Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据