Direct DNA binding by Brca1.

T T Paull; D Cortez; B Bowers; S J Elledge; M Gellert

doi:10.1073/pnas.111125998

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Direct DNA binding by Brca1.

T T Paull·D Cortez·B Bowers·S J Elledge·M Gellert

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Abstract

The tumor suppressor Brca1 plays an important role in protecting mammalian cells against genomic instability, but little is known about its modes of action. In this work we demonstrate that recombinant human Brca1 protein binds strongly to DNA, an activity conferred by a domain in the center of the Brca1 polypeptide. As a result of this binding, Brca1 inhibits the nucleolytic activities of the Mre11/Rad50/Nbs1 complex, an enzyme implicated in numerous aspects of double-strand break repair. Brca1 displays a preference for branched DNA structures and forms protein-DNA complexes cooperatively between multiple DNA strands, but without DNA sequence specificity. This fundamental property of Brca1 may be an important part of its role in DNA repair and transcription.

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Animals BRCA1 Protein Binding Sites Cell Cycle Proteins DNA DNA Damage DNA Repair DNA-Binding Proteins Exodeoxyribonucleases Genes, Tumor Suppressor Humans MRE11 Homologue Protein Nuclear Proteins Protein Binding Recombinant Fusion Proteins Journal Article Research Support, Non-U.S. Gov't

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T T Paull, D Cortez, B Bowers, S J Elledge, M Gellert. 2001-05-15. Direct DNA binding by Brca1.. https://doi.org/10.1073/pnas.111125998

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