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Journal article
FANCJ Uses Its Motor ATPase to Destabilize Protein-DNA Complexes, Unwind Triplexes, and Inhibit RAD51 Strand Exchange
The Journal of biological chemistry, v 284(12), pp 7505-7517
20 Mar 2009
PMID: 19150983
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mutations in the FANCJ helicase predispose individuals to breast cancer and are genetically linked to the Fanconi anemia (FA) complementation group J.FA is a chromosomal instability disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. FANCJ has been proposed to function downstream of FANCD2 monoubi-quitination, a critical event in the FA pathway. Evidence supports a role for FANCJ in a homologous recombination pathway of double strand break repair. In an effort to understand the molecular functions of FANCJ, we have investigated the ability of purified FANCJ recombinant protein to use its motor ATPase function for activities in addition to unwinding of conventional duplex DNA substrates. These efforts have led to the discovery that FANCJ ATP hydrolysis can be used to destabilize protein-DNA complexes and unwind triple helix alternate DNA structures. These novel catalytic functions of FANCJ may be important for its role in cellular DNA repair, recombination, or resolving DNA structural obstacles to replication. Consistent with this, we show that FANCJ can inhibit RAD51 strand exchange, an activity that is likely to be important for its role in controlling DNA repair through homologous recombination.
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Details
- Title
- FANCJ Uses Its Motor ATPase to Destabilize Protein-DNA Complexes, Unwind Triplexes, and Inhibit RAD51 Strand Exchange
- Creators
- Joshua A. Sommers - Laboratory of Molecular Gerontology, NIA, National Institutes of Health, National Institutes of Health Biomedical Research Center, Baltimore, Maryland 21224Nina Rawtani - Laboratory of Molecular Gerontology, NIA, National Institutes of Health, National Institutes of Health Biomedical Research Center, Baltimore, Maryland 21224Rigu Gupta - Laboratory of Molecular Gerontology, NIA, National Institutes of Health, National Institutes of Health Biomedical Research Center, Baltimore, Maryland 21224Dmitry V. Bugreev - Drexel UniversityAlexander V. Mazin - Drexel UniversitySharon B. Cantor - University of Massachusetts Medical SchoolRobert M. Brosh - Laboratory of Molecular Gerontology, NIA, National Institutes of Health, National Institutes of Health Biomedical Research Center, Baltimore, Maryland 21224
- Publication Details
- The Journal of biological chemistry, v 284(12), pp 7505-7517
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 13
- Grant note
- Fanconi Anemia Research Fund R01CA100839 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CA100839; MH084119 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA ZIAAG000741 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) NIA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) National Institutes of Health Intramural Research Program; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R03MH084119 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) 1054-09 / Leukemia and Lymphoma Society Scholar Award; Leukemia and Lymphoma Society
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000264195600014
- Scopus ID
- 2-s2.0-65549113446
- Other Identifier
- 991019168267104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology