Abstract
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 showthat 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.
Original language | English (US) |
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Pages (from-to) | 1469-1482 |
Number of pages | 14 |
Journal | Genes and Development |
Volume | 31 |
Issue number | 14 |
DOIs | |
State | Published - 2017 |
Keywords
- Abro1
- BRCA2
- DNA2
- MRE11
- RAD51
- Stalled replication fork stability
ASJC Scopus subject areas
- Genetics
- Developmental Biology
MD Anderson CCSG core facilities
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