Journal article
Novel function of the Fanconi anemia group J or RECQ1 helicase to disrupt protein-DNA complexes in a replication protein A-stimulated manner
The Journal of biological chemistry, Vol.289(29), pp.19928-19941
07/18/2014
DOI: 10.1074/jbc.M113.542456
PMCID: PMC4106313
PMID: 24895130
Abstract
Understanding how cellular machinery deals with chromosomal genome complexity is an important question because protein bound to DNA may affect various cellular processes of nucleic acid metabolism. DNA helicases are at the forefront of such processes, yet there is only limited knowledge how they remodel protein-DNA complexes and how these mechanisms are regulated. We have determined that representative human RecQ and Fe-S cluster DNA helicases are potently blocked by a protein-DNA interaction. The Fanconi anemia group J (FANCJ) helicase partners with the single-stranded DNA-binding protein replication protein A (RPA) to displace BamHI-E111A bound to duplex DNA in a specific manner. Protein displacement was dependent on the ATPase-driven function of the helicase and unique properties of RPA. Further biochemical studies demonstrated that the shelterin proteins TRF1 and TRF2, which preferentially bind the telomeric repeat found at chromosome ends, effectively block FANCJ from unwinding the forked duplex telomeric substrate. RPA, but not the Escherichia coli single-stranded DNA-binding protein or shelterin factor Pot1, stimulated FANCJ ejection of TRF1 from the telomeric DNA substrate. FANCJ was also able to displace TRF2 from the telomeric substrate in an RPA-dependent manner. The stimulation of helicase-catalyzed protein displacement is also observed with the DNA helicase RECQ1, suggesting a conserved functional interaction of RPA-interacting helicases. These findings suggest that partnerships between RPA and interacting human DNA helicases may greatly enhance their ability to dislodge proteins bound to duplex DNA, an activity that is likely to be highly relevant to their biological roles in DNA metabolism.
Details
- Title: Subtitle
- Novel function of the Fanconi anemia group J or RECQ1 helicase to disrupt protein-DNA complexes in a replication protein A-stimulated manner
- Creators
- Joshua A Sommers - From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224Taraswi Banerjee - From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224Twila Hinds - From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224Bingbing Wan - the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, andMarc S Wold - the Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Ming Lei - the Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, andRobert M Brosh Jr - From the Laboratory of Molecular Gerontology, Biomedical Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, broshr@mail.nih.gov
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.289(29), pp.19928-19941
- DOI
- 10.1074/jbc.M113.542456
- PMID
- 24895130
- PMCID
- PMC4106313
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- United States
- Grant note
- Intramural NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 07/18/2014
- Academic Unit
- Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984025268302771
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