期刊
GENES & DEVELOPMENT
卷 31, 期 14, 页码 1469-1482出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.299172.117
关键词
Abro1; BRCA2; DNA2; MRE11; RAD51; stalled replication fork stability
资金
- Cancer Prevention Research Institute of Texas (CPRIT) Graduate Scholar Award
- National Institutes of Health [CA155025]
- Mel Klein Family Fund
- University of Texas M.D. Anderson Cancer Center (Institutional Research Grant Program)
- [1R01CA164346]
- [1R01CA200703]
- [CPRIT RP140402]
Protection of the stalled replication fork is crucial for responding to replication stress and minimizing its impact on chromosome instability, thus preventing diseases, including cancer. We found a new component, Abro1, in the protection of stalled replication fork integrity. Abro1 deficiency results in increased chromosome instability, and Abro1-null mice are tumor-prone. We show that Abro1 protects stalled replication fork stability by inhibiting DNA2 nuclease/WRN helicase-mediated degradation of stalled forks. Depletion of RAD51 prevents the DNA2/WRN-dependent degradation of stalled forks in Abro1-deficient cells. This mechanism is distinct from the BRCA2-dependent fork protection pathway, in which stable RAD51 filament formation prevents MRE11-dependent degradation of the newly synthesized DNA at stalled forks. Thus, our data reveal a new aspect of regulated protection of stalled replication forks that involves Abro1.
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