Cited by 111DNA Repair MechanismsBRCA gene mutations in cancerCancer-related Molecular Pathways

Activation of BRCA1/BRCA2-Associated Helicase BACH1 Is Required for Timely Progression through S Phase

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Kumaraswamy, Easwari, Shiekhattar, Ramin·2007·Molecular and Cellular Biology

Abstract

BACH1 (also known as FANCJ and BRIP1) is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1. Previous biochemical and functional analyses have suggested a role for the BACH1 homolog in Caenorhabditis elegans during DNA replication. Here, we report the association of BACH1 with a distinct BRCA1/BRCA2-containing complex during the S phase of the cell cycle. Depletion of BACH1 or BRCA1 using small interfering RNAs results in delayed entry into the S phase of the cell cycle. Such timely progression through S phase requires the helicase activity of BACH1. Importantly, cells expressing a dominant negative mutation in BACH1 that results in a defective helicase displayed increased activation of DNA damage checkpoints and genomic instability. BACH1 helicase is silenced during the G(1) phase of the cell cycle and is activated through a dephosphorylation event as cells enter S phase. These results point to a critical role for BACH1 helicase activity not only in the timely progression through the S phase but also in maintaining genomic stability.

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Crossref · 10.1128/mcb.00961-07

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  • FANCJ helicase activity induced in S phase is required for FANCJ to promote S phase progression and possibly intra-S phase checkpoints.

    “FANCJ helicase activity induced in S phase is also required for FANCJ to promote S phase progression and possibly intra-S phase checkpoints [71,72].”

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Authors
Kumaraswamy, E., & Shiekhattar, R.
Affiliations
The Wistar Institute (US)
Venue
Molecular and Cellular Biology
Published
2007-10-01
Volume
27
Issue
19
Pages
6733-6741
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2138707085
Cited by
110
References
45
Citations by year
2026: 1 · 2025: 2 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 6 · 2012: 10
FWCI
5.43
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (CA90758, R01CA090758)
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 › Cancer-related Molecular Pathways
Keywords
BACH1, BRCA1, BRCA2, DNA helicase, S phase progression, cell cycle, BRCT domain, DNA damage checkpoint, genomic instability, dephosphorylation, G1 phase, Caenorhabditis elegans, dominant negative mutation
MeSH terms
Animals, Chromatin, DNA Damage, Enzyme Activation, Humans, S Phase, Caenorhabditis elegans, BRCA1 Protein, BRCA2 Protein, Tumor Suppressor Proteins, RNA, Small Interfering, Ubiquitin-Protein Ligases, Multiprotein Complexes, Basic-Leucine Zipper Transcription Factors, Fanconi Anemia Complementation Group Proteins

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