Document Detail

SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination.
MedLine Citation:
PMID:  19136956     Owner:  NLM     Status:  MEDLINE    
Several molecular mechanisms have been proposed to explain trinucleotide repeat expansions. Here we show that in yeast srs2Delta cells, CTG repeats undergo both expansions and contractions, and they show increased chromosomal fragility. Deletion of RAD52 or RAD51 suppresses these phenotypes, suggesting that recombination triggers trinucleotide repeat instability in srs2Delta cells. In sgs1Delta cells, CTG repeats undergo contractions and increased fragility by a mechanism partially dependent on RAD52 and RAD51. Analysis of replication intermediates revealed abundant joint molecules at the CTG repeats during S phase. These molecules migrate similarly to reversed replication forks, and their presence is dependent on SRS2 and SGS1 but not RAD51. Our results suggest that Srs2 promotes fork reversal in repetitive sequences, preventing repeat instability and fragility. In the absence of Srs2 or Sgs1, DNA damage accumulates and is processed by homologous recombination, triggering repeat rearrangements.
Alix Kerrest; Ranjith P Anand; Rangapriya Sundararajan; Rodrigo Bermejo; Giordano Liberi; Bernard Dujon; Catherine H Freudenreich; Guy-Franck Richard
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-01-11
Journal Detail:
Title:  Nature structural & molecular biology     Volume:  16     ISSN:  1545-9985     ISO Abbreviation:  Nat. Struct. Mol. Biol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-04     Completed Date:  2009-02-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101186374     Medline TA:  Nat Struct Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  159-67     Citation Subset:  IM    
Institut Pasteur, Unité de Génétique Moléculaire des Levures, CNRS, URA2171, Université Pierre et Marie Curie, UFR 927, 25 rue du Dr Roux, F-75015 Paris, France.
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MeSH Terms
Chromosome Breakage*
Chromosome Fragility
DNA Helicases / genetics,  metabolism*
DNA Replication
Gene Deletion
Rad51 Recombinase / genetics,  metabolism
Rad52 DNA Repair and Recombination Protein / genetics,  metabolism
RecQ Helicases / genetics,  metabolism*
Recombination, Genetic
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Trinucleotide Repeats
Grant Support
Reg. No./Substance:
0/RAD52 protein, S cerevisiae; 0/Rad52 DNA Repair and Recombination Protein; 0/Saccharomyces cerevisiae Proteins; 125481-05-2/HPR5 protein, S cerevisiae; EC 2.7.7.-/Rad51 Recombinase; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/RecQ Helicases; EC 3.6.1.-/SGS1 protein, S cerevisiae

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