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PMID: 14983014 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 8 ·2004-02-24 ·Pages 2357-62

Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM

Abstract

BACH1 is a nuclear protein that directly interacts with the highly conserved, C-terminal BRCT repeats of the tumor suppressor, BRCA1. Mutations within the BRCT repeats disrupt the interaction between BRCA1 and BACH1, lead to defects in DNA repair, and result in breast and ovarian cancer. BACH1 is necessary for efficient double-strand break repair in a manner that depends on its association with BRCA1. Moreover, some women with early-onset breast cancer and no abnormalities in either BRCA1 or BRCA2 carry germline BACH1 coding sequence changes, suggesting that abnormal BACH1 function contributes to tumor induction. Here, we show that BACH1 is both a DNA-dependent ATPase and a 5'-to-3' DNA helicase. In two patients with early-onset breast cancer who carry distinct germline BACH1 coding sequence changes, the resulting proteins are defective in helicase activity, indicating that these sequence changes disrupt protein function. These results reinforce the notion that mutant BACH1 participates in breast cancer development.

MeSH Terms
Adenosine Triphosphatases/metabolism Amino Acid Substitution BRCA1 Protein/metabolism Basic-Leucine Zipper Transcription Factors DNA Helicases/metabolism Fanconi Anemia Complementation Group Proteins Germ-Line Mutation Humans Leucine Zippers Mutagenesis, Site-Directed Nuclear Proteins/metabolism Transcription Factors/genetics,metabolism
Chemicals
BACH1 protein, human BRCA1 Protein Basic-Leucine Zipper Transcription Factors Fanconi Anemia Complementation Group Proteins Nuclear Proteins Transcription Factors Adenosine Triphosphatases DNA Helicases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cantor Sharon
Department of Cancer Biology, University of Massachusetts Medical School, Lazare Research Building, Worcester, MA 01605, USA.
Drapkin Ronny
Zhang Fan
Lin Yafang
Han Juliana
Pamidi Sushmita
Livingston David 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.0308717101
Published
2004-02-24
Pages
2357-62
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC356955
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1073/pnas.0308717101 PMC Full Text View journal details
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