The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress.
Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier (SUMO) in response to genotoxic stress, ... and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response.
Mesh Terms:
Animals, BRCA1 Protein, COS Cells, Cell Line, Cercopithecus aethiops, DNA Breaks, Double-Stranded, DNA Damage, DNA Repair, Hela Cells, Histones, Humans, Protein Inhibitors of Activated STAT, Small Ubiquitin-Related Modifier Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination
Animals, BRCA1 Protein, COS Cells, Cell Line, Cercopithecus aethiops, DNA Breaks, Double-Stranded, DNA Damage, DNA Repair, Hela Cells, Histones, Humans, Protein Inhibitors of Activated STAT, Small Ubiquitin-Related Modifier Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases, Ubiquitination
Nature
Date: Dec. 17, 2009
PubMed ID: 20016594
View in: Pubmed Google Scholar
Download Curated Data For This Publication
101110
Switch View:
- Interactions 7
- PTM Genes 1