Document Detail


Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage.
MedLine Citation:
PMID:  15975089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Members of the RecQ family of DNA helicases, mutated in several syndromes associated with cancer predisposition, are key regulators of genome stability. The Saccharomyces cerevisiae SLX4 gene is required for cell viability in the absence of Sgs1, the only yeast RecQ helicase. SLX4 encodes one subunit of the heterodimeric Slx1-Slx4 endonuclease, although its cellular function is not clear. Slx1-Slx4 was reported to preferentially cleave replication fork-like structures in vitro, and cells lacking SLX4 are hypersensitive to DNA alkylation damage. Here we report that Slx4 becomes phosphorylated in cells exposed to a wide range of genotoxins. Even though it has been proposed that the role of Slx4 is restricted to S-phase, Slx4 phosphorylation is observed in cells arrested in G1 or G2 phases of the cell cycle, but not during an unperturbed cell cycle. Slx4 phosphorylation is completely abolished in cells lacking the Mec1 and Tel1 protein kinases, critical regulators of genome stability, but is barely affected in the absence of both Rad53 and Chk1 kinases. Finally we show that, whereas both Slx1 and Slx4 are dispensable for activation of cell-cycle checkpoints, Slx4, but not Slx1, is required for repair of DNA alkylation damage in both aynchronously growing cells and in G2-phase-arrested cells. These results reveal Slx4 as a new target of the Mec1/Tel1 kinases, with a crucial role in DNA repair that is not restricted to the processing of stalled replisomes.
Authors:
Sonja Flott; John Rouse
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  391     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2006-01-26     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  325-33     Citation Subset:  IM    
Affiliation:
MRC Protein Phosphorylation Unit, Medical Sciences Institute/Wellcome Trust Biocentre Complex, Dow St., University of Dundee, Dundee DD1 5EH, Scotland, UK.
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MeSH Terms
Descriptor/Qualifier:
Alkylation
Cell Cycle Proteins / genetics
Cell Division / genetics
DNA Damage*
DNA Repair*
DNA, Fungal / metabolism*
Endodeoxyribonucleases / genetics,  metabolism*
Fungal Proteins / genetics,  metabolism*
Gene Deletion
Gene Expression Regulation, Fungal
Intracellular Signaling Peptides and Proteins
Mutagens / pharmacology
Phosphorylation
Protein Kinases / genetics
Protein-Serine-Threonine Kinases / genetics
Saccharomyces cerevisiae / cytology,  drug effects,  genetics*
Saccharomyces cerevisiae Proteins / genetics,  metabolism*
Signal Transduction
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA, Fungal; 0/Fungal Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Mutagens; 0/Saccharomyces cerevisiae Proteins; EC 2.7.-/Protein Kinases; EC 2.7.1.-/RAD53 protein, S cerevisiae; EC 2.7.11.1/Checkpoint kinase 1; EC 2.7.11.1/MEC1 protein, S cerevisiae; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/TEL1 protein, S cerevisiae; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.-/SLX1 protein, S cerevisiae; EC 3.1.-/SLX4 protein, S cerevisiae
Comments/Corrections

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