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PMID: 11353843 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Direct DNA binding by Brca1.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 11 ·2001-05-22 ·Pages 6086-91

Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M

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.

MeSH Terms
Animals BRCA1 Protein/metabolism,physiology Binding Sites Cell Cycle Proteins/metabolism DNA/metabolism DNA Damage DNA Repair DNA-Binding Proteins/metabolism Exodeoxyribonucleases/metabolism Genes, Tumor Suppressor Humans MRE11 Homologue Protein Nuclear Proteins Protein Binding Recombinant Fusion Proteins/metabolism,physiology
Chemicals
BRCA1 Protein Cell Cycle Proteins DNA-Binding Proteins MRE11 protein, human NBN protein, human Nuclear Proteins Recombinant Fusion Proteins DNA Exodeoxyribonucleases MRE11 Homologue Protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Paull T T
Department of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA. [email protected]
Cortez D
Bowers B
Elledge S J
Gellert M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.111125998
Email
[email protected]
Published
2001-05-22
Epub
2001-00-15
Pages
6086-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC33426
Subset
IM
Corrections
CommentIn
PMID: 11371630
External Links
PubMed source DOI: 10.1073/pnas.111125998 PMC Full Text View journal details
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