期刊
CELL CYCLE
卷 12, 期 18, 页码 3037-3051出版社
LANDES BIOSCIENCE
DOI: 10.4161/cc.26078
关键词
E2F; transcription; DNA damage; DNA repair; somatic mutation
类别
资金
- CRUK [C300/A13058]
- MRC
- Cancer Research UK [13058] Funding Source: researchfish
- Medical Research Council [G1000807, G0500905, G9400953] Funding Source: researchfish
- MRC [G0500905, G9400953, G1000807] Funding Source: UKRI
The cellular response to DNA damage, mediated by the DNA repair process, is essential in maintaining the integrity and stability of the genome. E2F-7 is an atypical member of the E2F family with a role in negatively regulating transcription and cell cycle progression under DNA damage. Surprisingly, we found that E2F-7 makes a transcription-independent contribution to the DNA repair process, which involves E2F-7 locating to and binding damaged DNA. Further, E2F-7 recruits CtBP and HDAC to the damaged DNA, altering the local chromatin environment of the DNA lesion. Importantly, the E2F-7 gene is a target for somatic mutation in human cancer and tumor-derived mutant alleles encode proteins with compromised transcription and DNA repair properties. Our results establish that E2F-7 participates in 2 closely linked processes, allowing it to directly couple the expression of genes involved in the DNA damage response with the DNA repair machinery, which has relevance in human malignancy.
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