FANCJ Is a Structure-specific DNA Helicase Associated with the Maintenance of Genomic G/C Tracts
Open accessAbstract
Fanconi anemia (FA) is a heritable human cancer-susceptibility disorder, delineating a genetically heterogenous pathway for the repair of replication-blocking lesions such as interstrand DNA cross-links. Here we demonstrate that one component of this pathway, FANCJ, is a structure-specific DNA helicase that dissociates guanine quadruplex DNA (G4 DNA) in vitro. Moreover, in contrast with previously identified G4 DNA helicases, such as the Bloom's helicase (BLM), FANCJ unwinds G4 substrates with 5'-3' polarity. In the FA-J human patient cell line EUFA0030 the loss of FANCJ G4 unwinding function correlates with the accumulation of large genomic deletions in the vicinity of sequences, which match the G4 DNA signature. Together these findings support a role for FANCJ in the maintenance of potentially unstable genomic G/C tracts during replication.
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FA-J patient cells accumulate deletions in regions containing G4-DNA, and recombinant FANCJ A349P fails to unwind G4-DNA substrates.
“In support of this function, FA-J patient cells accumulate deletions in regions containing G4-DNA, and the recombinant FANCJ A349P mutant protein fails to unwind G4-DNA substrates [42,79].”
From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [79]
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- Authors
- London, T. B. C., Barber, L. J., Mosedale, G., Kelly, G. P., Balasubramanian, S., Hickson, I. D., Boulton, S. J., & Hiom, K.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Cancer Research UK (GB)
- John Radcliffe Hospital (GB)
- University of Cambridge (GB)
- Corresponding author
- Hiom, Kevin
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 283
- Issue
- 52
- Pages
- 36132-36139
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2662291
- OpenAlex
- W2067133520
- Cited by
- 252
- References
- 28
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 14 · 2023: 14 · 2022: 7 · 2021: 18 · 2020: 16 · 2019: 12 · 2018: 10 · 2017: 13 · 2016: 18 · 2015: 14 · 2014: 21 · 2013: 13 · 2012: 13
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- Cancer Research UK (A5709)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- FANCJ, Fanconi anemia, DNA helicase, genomic instability, genomic deletions, interstrand cross-links, DNA replication
- MeSH terms
- Binding, Competitive, Cell Line, Cross-Linking Reagents, DNA Replication, DNA Helicases, Humans, Nucleic Acid Conformation, Nucleic Acid Hybridization, Genome, Gene Deletion, Genetic Predisposition to Disease, Cell Line, Tumor, Basic-Leucine Zipper Transcription Factors, Fanconi Anemia Complementation Group Proteins, RecQ Helicases, G-Quadruplexes
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