BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks.
The BRCA1 tumor suppressor has been implicated in the maintenance of chromosomal stability through homology-directed repair of DNA double-strand breaks. Much of the BRCA1 in cells forms a heterodimeric complex with a structurally related protein BARD1. We report that expression of truncated mouse or human BARD1 peptides capable of interacting with Brca1 results in a homologous-repair deficiency. Repair is mildly reduced in Brca1 wild-type cells and severely reduced in cells that harbor a Brca1 splice product deleted for exon 11. Nuclear localization of the Brca1 or BARD1 peptides is not compromised, implying that the repair deficiency is caused by a more direct effect on repair. The tumor suppressor activity of BRCA1 may require the participation of BARD1 to maintain chromosome integrity through the homologous-repair pathway.
Westermark
Ulrica K
UK
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Reyngold
Marsha
M
Olshen
Adam B
AB
Baer
Richard
R
Jasin
Maria
M
Moynahan
Mary Ellen
ME
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002875:Chromosomes / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D017930:Genes, Reporter; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D016685:Mitomycin / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
D019313:BRCA1 Protein; D002352:Carrier Proteins; D046911:Macromolecular Substances; D019384:Nucleic Acid Synthesis Inhibitors; D010455:Peptides; D025521:Tumor Suppressor Proteins; D016685:Mitomycin; C102449:BARD1 protein, human; C491163:Bard1 protein, mouse; D044767:Ubiquitin-Protein Ligases