Direct DNA binding by Brca1.
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.
Paull
T T
TT
Department of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA. tpaull@icmb.utexas.edu
Cortez
D
D
Bowers
B
B
Elledge
S J
SJ
Gellert
M
M
D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000502:physiology
D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D004247:DNA; D005090:Exodeoxyribonucleases; D000076228:MRE11 Homologue Protein