RAP80, ubiquitin and SUMO in the DNA damage response
- Resource Type
- Review Paper
- Authors
- Lombardi, Patrick M.; Matunis, Michael J.; Wolberger, Cynthia
- Source
- Journal of Molecular Medicine. August 2017 95(8):799-807
- Subject
- RAP80
DNA double-strand break repair
Homologous recombination
BRCA1
Ubiquitin
SUMO
- Language
- English
- ISSN
- 0946-2716
1432-1440
A decade has passed since the first reported connection between RAP80 and BRCA1 in DNA double-strand break repair. Despite the initial identification of RAP80 as a factor localizing BRCA1 to DNA double-strand breaks and potentially promoting homologous recombination, there is increasing evidence that RAP80 instead suppresses homologous recombination to fine-tune the balance of competing DNA repair processes during the S/G2 phase of the cell cycle. RAP80 opposes homologous recombination by inhibiting DNA end-resection and sequestering BRCA1 into the BRCA1-A complex. Ubiquitin and SUMO modifications of chromatin at DNA double-strand breaks recruit RAP80, which contains distinct sequence motifs that recognize ubiquitin and SUMO. Here, we review RAP80’s role in repressing homologous recombination at DNA double-strand breaks and how this role is facilitated by its ability to bind ubiquitin and SUMO modifications.