Involvement of p54(nrb), a PSF partner protein, in DNA double-strand break repair and radioresistance.

Hdl Handle:
http://hdl.handle.net/10675.2/149
Title:
Involvement of p54(nrb), a PSF partner protein, in DNA double-strand break repair and radioresistance.
Authors:
Li, Shuyi; Kuhne, Wendy W.; Kulharya, Anita; Hudson, Farlyn Z; Ha, Kyungsoo; Cao, Zhen; Dynan, William S. ( 0000-0002-4045-5662 )
Abstract:
Mammalian cells repair DNA double-strand breaks (DSBs) via efficient pathways of direct, nonhomologous DNA end joining (NHEJ) and homologous recombination (HR). Prior work has identified a complex of two polypeptides, PSF and p54(nrb), as a stimulatory factor in a reconstituted in vitro NHEJ system. PSF also stimulates early steps of HR in vitro. PSF and p54(nrb) are RNA recognition motif-containing proteins with well-established functions in RNA processing and transport, and their apparent involvement in DSB repair was unexpected. Here we investigate the requirement for p54(nrb) in DSB repair in vivo. Cells treated with siRNA to attenuate p54(nrb) expression exhibited a delay in DSB repair in a gamma-H2AX focus assay. Stable knockdown cell lines derived by p54(nrb) miRNA transfection showed a significant increase in ionizing radiation-induced chromosomal aberrations. They also showed increased radiosensitivity in a clonogenic survival assay. Together, results indicate that p54(nrb) contributes to rapid and accurate repair of DSBs in vivo in human cells and that the PSF.p54(nrb) complex may thus be a potential target for radiosensitizer development.
Citation:
Nucleic Acids Res. 2009 Nov; 37(20):6746-6753
Issue Date:
16-Nov-2009
URI:
http://hdl.handle.net/10675.2/149
DOI:
10.1093/nar/gkp741
PubMed ID:
19759212
PubMed Central ID:
PMC2777424
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
ISSN:
1362-4962
Appears in Collections:
Department of Pathology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Shuyien_US
dc.contributor.authorKuhne, Wendy W.en_US
dc.contributor.authorKulharya, Anitaen_US
dc.contributor.authorHudson, Farlyn Zen_US
dc.contributor.authorHa, Kyungsooen_US
dc.contributor.authorCao, Zhenen_US
dc.contributor.authorDynan, William S.en_US
dc.date.accessioned2010-09-24T22:03:28Z-
dc.date.available2010-09-24T22:03:28Z-
dc.date.issued2009-11-16en_US
dc.identifier.citationNucleic Acids Res. 2009 Nov; 37(20):6746-6753en_US
dc.identifier.issn1362-4962en_US
dc.identifier.pmid19759212en_US
dc.identifier.doi10.1093/nar/gkp741en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/149-
dc.description.abstractMammalian cells repair DNA double-strand breaks (DSBs) via efficient pathways of direct, nonhomologous DNA end joining (NHEJ) and homologous recombination (HR). Prior work has identified a complex of two polypeptides, PSF and p54(nrb), as a stimulatory factor in a reconstituted in vitro NHEJ system. PSF also stimulates early steps of HR in vitro. PSF and p54(nrb) are RNA recognition motif-containing proteins with well-established functions in RNA processing and transport, and their apparent involvement in DSB repair was unexpected. Here we investigate the requirement for p54(nrb) in DSB repair in vivo. Cells treated with siRNA to attenuate p54(nrb) expression exhibited a delay in DSB repair in a gamma-H2AX focus assay. Stable knockdown cell lines derived by p54(nrb) miRNA transfection showed a significant increase in ionizing radiation-induced chromosomal aberrations. They also showed increased radiosensitivity in a clonogenic survival assay. Together, results indicate that p54(nrb) contributes to rapid and accurate repair of DSBs in vivo in human cells and that the PSF.p54(nrb) complex may thus be a potential target for radiosensitizer development.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshCell Survivalen_US
dc.subject.meshChromosome Aberrationsen_US
dc.subject.meshDNA Breaks, Double-Strandeden_US
dc.subject.meshDNA Repairen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHumansen_US
dc.subject.meshNuclear Matrix-Associated Proteins / metabolismen_US
dc.subject.meshOctamer Transcription Factors / metabolismen_US
dc.subject.meshRNA, Small Interfering / metabolismen_US
dc.subject.meshRNA-Binding Proteins / metabolismen_US
dc.subject.meshRadiation Toleranceen_US
dc.titleInvolvement of p54(nrb), a PSF partner protein, in DNA double-strand break repair and radioresistance.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.typeResearch Support, U.S. Gov't, P.H.S.en_US
dc.identifier.pmcidPMC2777424en_US
dc.contributor.corporatenameDepartment of Pathologyen_US

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