Document Detail


Homologous recombination resolution defect in werner syndrome.
MedLine Citation:
PMID:  12242278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Werner syndrome (WRN) is an uncommon autosomal recessive disease whose phenotype includes features of premature aging, genetic instability, and an elevated risk of cancer. We used three different experimental strategies to show that WRN cellular phenotypes of limited cell division potential, DNA damage hypersensitivity, and defective homologous recombination (HR) are interrelated. WRN cell survival and the generation of viable mitotic recombinant progeny could be rescued by expressing wild-type WRN protein or by expressing the bacterial resolvase protein RusA. The dependence of WRN cellular phenotypes on RAD51-dependent HR pathways was demonstrated by using a dominant-negative RAD51 protein to suppress mitotic recombination in WRN and control cells: the suppression of RAD51-dependent recombination led to significantly improved survival of WRN cells following DNA damage. These results define a physiological role for the WRN RecQ helicase protein in RAD51-dependent HR and identify a mechanistic link between defective recombination resolution and limited cell division potential, DNA damage hypersensitivity, and genetic instability in human somatic cells.
Authors:
Yannick Saintigny; Kate Makienko; Cristina Swanson; Mary J Emond; Raymond J Monnat
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  22     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-20     Completed Date:  2002-10-30     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6971-8     Citation Subset:  IM    
Affiliation:
Departments of Pathology. Biostatistics. Genome Sciences, University of Washington, Seattle, Washington 98195-7705, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Division
Cell Line, Transformed
DNA Damage
DNA Helicases / genetics*,  metabolism
DNA-Binding Proteins / genetics,  metabolism*
Exodeoxyribonucleases
Humans
Rad51 Recombinase
RecQ Helicases
Recombination, Genetic*
Werner Syndrome / genetics*
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; EC 2.7.7.-/RAD51 protein, human; EC 2.7.7.-/Rad51 Recombinase; EC 3.1.-/Exodeoxyribonucleases; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/RecQ Helicases; EC 3.6.1.-/WRN protein, human
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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