CoChat
Sign Up
Cited by 240DNA Repair MechanismsBRCA gene mutations in cancerPARP inhibition in cancer therapy

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

Open access
Cantor, Sharon, Drapkin, Ronny, Zhang, Fan, Lin, Yafang, Han, Juliana, Pamidi, Sushmita, Livingston, David M.·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0308717101PMC PMC356955
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1073/pnas.0308717101

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The P47A variant, shown to disrupt FANCJ enzyme function, was found in controls of a later study and considered unrelated to breast cancer.

    “For example, the P47A variant identified in 2001 [8] and shown to disrupt FANCJ enzyme function [56] was found in the controls of a subsequent study and considered to be unrelated to breast cancer [44].”

    From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [56]

  • The ATPase and helicase functions of FANCJ are inactivated by the K52R missense mutation in the ATP-binding pocket.

    “As predicted, the ATPase and helicase functions were inactivated by a single missense mutation (K52R) in the ATP-binding pocket of the FANCJ helicase domain [56,61,62].”

    From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [56]

  • Wild-type FANCJ is a DNA-dependent ATPase that unwinds DNA in a 5′ to 3′ direction.

    “These studies revealed that wild-type FANCJ is a DNA-dependent ATPase, which unwinds DNA in a 5′ to 3′ direction [56].”

    From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [56]

  • The breast cancer-associated P47A mutation and the FA-associated A349P mutation reduce FANCJ enzyme activity.

    “Consistent with enzyme activity being essential for tumor suppression, the breast cancer-associated mutation in helicase block II (P47A) or an FA-associated mutation in the Fe–S domain (A349P) reduced FANCJ enzyme activity [42,56,63].”

    From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [56]

  • The P47A FANCJ mutant has disrupted enzyme activity.

    “The P47A mutant had disrupted enzyme activity”

    From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [56]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Cantor, S., Drapkin, R., Zhang, F., Lin, Y., Han, J., Pamidi, S., & Livingston, D. M.
Affiliations
Harvard University (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2004-02-17
Volume
101
Issue
8
Pages
2357-2362
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0308717101
PMC
PMC356955
OpenAlex
W2122003098
Cited by
240
References
44
Citations by year
2026: 7 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 7 · 2021: 11 · 2020: 9 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 6 · 2015: 10 · 2014: 12 · 2013: 14 · 2012: 13
FWCI
5.80
Type
journal article
Language
en
Update notices
correction (2004-04-27)
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Keywords
BACH1, BRCA1, DNA helicase, DNA-dependent ATPase, germline mutations, early-onset breast cancer, ovarian cancer, DNA double-strand break repair, DNA repair, protein-protein interaction, hereditary cancer predisposition
MeSH terms
Adenosine Triphosphatases, DNA Helicases, Humans, Nuclear Proteins, Transcription Factors, Mutagenesis, Site-Directed, Leucine Zippers, Germ-Line Mutation, BRCA1 Protein, Amino Acid Substitution, Basic-Leucine Zipper Transcription Factors, Fanconi Anemia Complementation Group Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review