Authors: | Westermark, U. K.; Reyngold, M.; Olshen, A. B.; Baer, R.; Jasin, M.; Moynahan, M. E. |
Article Title: | BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks |
Abstract: | 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. |
Keywords: | controlled study; protein expression; unclassified drug; exon; gene deletion; nonhuman; protein function; animal cell; animals; mice; mice, knockout; dna damage; homologous recombination; complex formation; dna repair; protein protein interaction; cell protein; cell line; protein binding; gene function; intracellular transport; peptide; brca1 protein; wild type; animalia; dna strand breakage; molecular cloning; cancer inhibition; oncogene; tumor suppressor gene; double stranded dna; carrier proteins; tumor suppressor proteins; protein transport; peptides; chromosome breakage; genes, reporter; protein structure; mitomycin; ubiquitin-protein ligases; chromosomes; rna splicing; macromolecular substances; molecular stability; brca1 associated ring domain protein 1; nucleic acid synthesis inhibitors; humans; priority journal; article |
Journal Title: | Molecular and Cellular Biology |
Volume: | 23 |
Issue: | 21 |
ISSN: | 0270-7306 |
Publisher: | American Society for Microbiology |
Date Published: | 2003-11-01 |
Start Page: | 7926 |
End Page: | 7936 |
Language: | English |
DOI: | 10.1128/mcb.23.21.7926-7936.2003 |
PUBMED: | 14560035 |
PROVIDER: | scopus |
PMCID: | PMC207645 |
DOI/URL: | |
Notes: | Export Date: 12 September 2014 -- Source: Scopus |