期刊
JOURNAL OF CELL BIOLOGY
卷 201, 期 5, 页码 693-707出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201302145
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资金
- Mary Kay Foundation [008-10]
- Public Health Service grants from the National Cancer Institute [P01-CA097403, R01-CA137023, R01-CA120954]
- National Cancer Institute [T32-CA09503]
- DoD Breast Cancer Research Program [BC083089]
- CDMRP [BC083089, 544554] Funding Source: Federal RePORTER
The CtIP protein facilitates homology-directed repair (HDR) of double-strand DNA breaks (DSBs) by initiating DNA resection, a process in which DSB ends are converted into 3.-ssDNA overhangs. The BRCA1 tumor suppressor, which interacts with CtIP in a phosphodependent manner, has also been implicated in DSB repair through the HDR pathway. It was recently reported that the BRCA1-CtIP interaction is essential for HDR in chicken DT40 cells. To examine the role of this interaction in mammalian cells, we generated cells and mice that express Ctip polypeptides (Ctip-S326A) that fail to bind BRCA1. Surprisingly, isogenic lines of Ctip-S326A mutant and wild-type cells displayed comparable levels of HDR function and chromosomal stability. Although Ctip-S326A mutant cells were modestly sensitive to topoisomerase inhibitors, mice expressing Ctip-S326A polypeptides developed normally and did not exhibit a predisposition to cancer. Thus, in mammals, the phospho-dependent BRCA1-CtIP interaction is not essential for HDR-mediated DSB repair or for tumor suppression.
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