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Article: Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2.

TitleEnhancement of RAD51 recombinase activity by the tumor suppressor PALB2.
Authors
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nsmb/
Citation
Nature Structural and Molecular Biology, 2010, v. 17 n. 10, p. 1255-1259 How to Cite?
AbstractHomologous recombination mediated by RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-strand breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2: to enhance RAD51's ability to form the D loop. We show that PALB2 binds DNA and physically interacts with RAD51. Notably, although PALB2 alone stimulates D-loop formation, it has a cooperative effect with RAD51AP1, an enhancer of RAD51. This stimulation stems from the ability of PALB2 to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results demonstrate the multifaceted role of PALB2 in chromosome damage repair. Because PALB2 mutations can cause cancer or Fanconi anemia, our findings shed light on the mechanism of tumor suppression in humans.
Persistent Identifierhttp://hdl.handle.net/10722/135014
ISSN
2015 Impact Factor: 13.338
2015 SCImago Journal Rankings: 12.548
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
US National Institutes of HealthRO1CA120315
RO1ES07061
RO1ES015252
RO1ES015632
PO1CA129186
PO1CA92584
Susan G. Komen for the Cure FoundationPDF0706844
Funding Information:

We are grateful to R. Buisson and J.-Y. Masson (Centre de Recherche du Centre hospitalier universitaire de Quebec) for the communication of results before publication, to S. Begovic, S. Longerich and Y.-C. Kim (Yale University) for assistance, to Y. Kwon (Yale University) for providing ScRad51 protein and to B. Xia (Department of Radiation Oncology, The Cancer Institute of NJ) for providing PALB2-deficient and PALB2-complemented cells, as well as for providing PALB2 antibody. This study was supported by research and program project grants RO1CA120315, RO1ES07061, RO1ES015252, RO1ES015632, PO1CA129186 and PO1CA92584 from the US National Institutes of Health and by postdoctoral fellowship PDF0706844 from the Susan G. Komen for the Cure Foundation.

 

DC FieldValueLanguage
dc.contributor.authorDray, Een_US
dc.contributor.authorEtchin, Jen_US
dc.contributor.authorwiese, Cen_US
dc.contributor.authorSaro, Den_US
dc.contributor.authorWilliams, GJen_US
dc.contributor.authorHammel, Men_US
dc.contributor.authorYu, Xen_US
dc.contributor.authorGalkin, VEen_US
dc.contributor.authorLiu, Den_US
dc.contributor.authorTsai, MSen_US
dc.contributor.authorSy, SMHen_US
dc.contributor.authorSchild, Den_US
dc.contributor.authorEgelman, Een_US
dc.contributor.authorChen, Jen_US
dc.contributor.authorSung, Pen_US
dc.date.accessioned2011-07-27T01:25:50Z-
dc.date.available2011-07-27T01:25:50Z-
dc.date.issued2010en_US
dc.identifier.citationNature Structural and Molecular Biology, 2010, v. 17 n. 10, p. 1255-1259en_US
dc.identifier.issn1545-9993-
dc.identifier.urihttp://hdl.handle.net/10722/135014-
dc.description.abstractHomologous recombination mediated by RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-strand breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2: to enhance RAD51's ability to form the D loop. We show that PALB2 binds DNA and physically interacts with RAD51. Notably, although PALB2 alone stimulates D-loop formation, it has a cooperative effect with RAD51AP1, an enhancer of RAD51. This stimulation stems from the ability of PALB2 to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results demonstrate the multifaceted role of PALB2 in chromosome damage repair. Because PALB2 mutations can cause cancer or Fanconi anemia, our findings shed light on the mechanism of tumor suppression in humans.-
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nsmb/-
dc.relation.ispartofNature Structural and Molecular Biologyen_US
dc.subject.meshBreast Neoplasms - metabolism-
dc.subject.meshDNA, Neoplasm - metabolism-
dc.subject.meshDNA-Binding Proteins - chemistry - physiology-
dc.subject.meshNuclear Proteins - chemistry - genetics - physiology-
dc.subject.meshTumor Suppressor Proteins - chemistry - genetics - physiology-
dc.titleEnhancement of RAD51 recombinase activity by the tumor suppressor PALB2.en_US
dc.typeArticleen_US
dc.identifier.emailSy, SMH: mhsy@hku.hken_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/nsmb.1916-
dc.identifier.pmid20871616-
dc.identifier.pmcidPMC2950913-
dc.identifier.scopuseid_2-s2.0-77957761350-
dc.identifier.hkuros186751en_US
dc.identifier.volume17en_US
dc.identifier.issue10-
dc.identifier.spage1255en_US
dc.identifier.epage1259en_US
dc.identifier.isiWOS:000282563600016-
dc.publisher.placeUnited States-
dc.identifier.citeulike7959111-

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