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PMID:12527904

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Citation

Wong, JM, Ionescu, D and Ingles, CJ (2003) Interaction between BRCA2 and replication protein A is compromised by a cancer-predisposing mutation in BRCA2. Oncogene 22:28-33

Abstract

Mutations in the BRCA1 and BRCA2 genes predispose women to familial, early-onset breast cancer. Both the BRCA1 and BRCA2 proteins appear to function in the homologous recombination pathway of DNA double-strand break repair. Both BRCA1 and BRCA2 have also been implicated in transcription by RNA polymerase II, for both proteins have domains which, when tethered adjacent to a promoter, can activate transcription. In experiments reported here, we have used protein affinity chromatography and coimmunoprecipitation techniques to show that the putative N-terminal acidic transcriptional activation domain of BRCA2 interacts with replication protein A (RPA), a protein essential for DNA repair, replication and recombination. This interaction was not mediated by DNA and was specific for human RPA but not yeast RPA. Since the cancer-predisposing mutation Y42C in BRCA2 significantly compromised the interaction between RPA and BRCA2, this interaction may be biologically important. That BRCA2 protein in HeLa cell extract also coimmunoprecipitated with RPA suggested that this interaction occurs in vivo. Therefore, the transcriptional activation domains within BRCA2, and perhaps BRCA1, may provide links to RPA and DNA repair processes rather than transcription.

Links

PubMed Online version:10.1038/sj.onc.1206071

Keywords

BRCA2 Protein/genetics; BRCA2 Protein/metabolism; Breast Neoplasms/genetics; Chromatography, Affinity; DNA-Binding Proteins/metabolism; Genetic Predisposition to Disease; Humans; Mutation; Precipitin Tests; Protein Binding; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Replication Protein A

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:RFA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P23025

F

Seeded From UniProt

complete

HUMAN:RFA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P27694

F

Seeded From UniProt

complete

HUMAN:XPA

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15927

F

Seeded From UniProt

complete

HUMAN:RFA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15927

F

Seeded From UniProt

complete

HUMAN:RFA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35244

F

Seeded From UniProt

complete

HUMAN:RFA3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P27694

F

Seeded From UniProt

complete


See also

References

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