Activation of BRCA1/BRCA2-Associated Helicase BACH1 Is Required for Timely Progression through S Phase
Open accessAbstract
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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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].”
From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [71]
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- Authors
- Kumaraswamy, E., & Shiekhattar, R.
- Affiliations
- The Wistar Institute (US)
- ORCID
- Shiekhattar, Ramin
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-10-01
- Volume
- 27
- Issue
- 19
- Pages
- 6733-6741
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2099226
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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