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The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA
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The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA
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Journal Article
The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA
2010
Overview
Tumor suppressor protein BRCA2 interacts with RAD51 and functions in homologous recombination, but understanding its precise functions has been hampered by difficulties in purifying such a large protein. Now purified full-length human BRCA2 is shown to bind selectively to ssDNA, to promote RAD51 binding to ssDNA while reducing its association with dsDNA, and to stimulate RAD51-mediated DNA strand exchange.
Individuals with
BRCA2
mutations are predisposed to breast cancers owing to genome instability. To determine the functions of BRCA2, the human protein was purified. It was found to bind selectively to single-stranded DNA (ssDNA), and to ssDNA in tailed duplexes and replication fork structures. Monomeric and dimeric forms of BRCA2 were observed by EM. BRCA2 directed the binding of RAD51 recombinase to ssDNA, reduced the binding of RAD51 to duplex DNA and stimulated RAD51-mediated DNA strand exchange. These observations provide a molecular basis for the role of BRCA2 in the maintenance of genome stability.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Apoptosis Regulatory Proteins
/ Biomedical and Life Sciences
/ BRCA2 Protein - ultrastructure
/ Breast Neoplasms - metabolism
/ Cancer
/ DNA
/ DNA, Single-Stranded - metabolism
/ Female
/ Genomics
/ Humans
/ Mutation
/ Neoplasm Proteins - chemistry
/ Neoplasm Proteins - physiology
/ Rad51 Recombinase - chemistry
/ Rad51 Recombinase - physiology
