Document Detail


Mutations in Mre11 phosphoesterase motif I that impair Saccharomyces cerevisiae Mre11-Rad50-Xrs2 complex stability in addition to nuclease activity.
MedLine Citation:
PMID:  16143598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Mre11-Rad50-Xrs2 complex is involved in DNA double-strand break repair, telomere maintenance, and the intra-S phase checkpoint. The Mre11 subunit has nuclease activity in vitro, but the role of the nuclease in DNA repair and telomere maintenance remains controversial. We generated six mre11 alleles with substitutions of conserved residues within the Mre11-phosphoesterase motifs and compared the phenotypes conferred, as well as exonuclease activity and complex formation, by the mutant proteins. Substitutions of Asp16 conferred the most severe DNA repair and telomere length defects. Interactions between Mre11-D16A or Mre11-D16N and Rad50 or Xrs2 were severely compromised, whereas the mre11 alleles with greater DNA repair proficiency also exhibited stable complex formation. At all of the targeted residues, alanine substitution resulted in a more severe defect in DNA repair compared to the more conservative asparagine substitutions, but all of the mutant proteins exhibited <2% of the exonuclease activity observed for wild-type Mre11. Our results show that the structural integrity of the Mre11-Rad50-Xrs2 complex is more important than the catalytic activity of the Mre11 nuclease for the overall functions of the complex in vegetative cells.
Authors:
Berit O Krogh; Bertrand Llorente; Alicia Lam; Lorraine S Symington
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-09-02
Journal Detail:
Title:  Genetics     Volume:  171     ISSN:  0016-6731     ISO Abbreviation:  Genetics     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-22     Completed Date:  2006-10-06     Revised Date:  2014-09-16    
Medline Journal Info:
Nlm Unique ID:  0374636     Medline TA:  Genetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1561-70     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
DNA Repair*
DNA-Binding Proteins / metabolism
Endodeoxyribonucleases / genetics*
Exodeoxyribonucleases / genetics*
Exonucleases / metabolism
Gamma Rays
Hydroxyurea
Immunoprecipitation
Methyl Methanesulfonate
Multiprotein Complexes / genetics,  metabolism*
Mutation / genetics*
Saccharomyces cerevisiae / genetics*
Saccharomyces cerevisiae Proteins / genetics*,  metabolism
Telomere / genetics
Grant Support
ID/Acronym/Agency:
GM 41784/GM/NIGMS NIH HHS; R01 GM041784/GM/NIGMS NIH HHS; R01 GM041784-16/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Multiprotein Complexes; 0/RAD50 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 0/XRS2 protein, S cerevisiae; AT5C31J09G/Methyl Methanesulfonate; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.-/Exodeoxyribonucleases; EC 3.1.-/Exonucleases; EC 3.1.-/MRE11 protein, S cerevisiae; X6Q56QN5QC/Hydroxyurea
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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