Modulation of the DNA-binding activity of Saccharomyces cerevisiae MSH2-MSH6 complex by the high-mobility group protein NHP6A, in vitro.

Hdl Handle:
http://hdl.handle.net/10675.2/69
Title:
Modulation of the DNA-binding activity of Saccharomyces cerevisiae MSH2-MSH6 complex by the high-mobility group protein NHP6A, in vitro.
Authors:
Labazi, Mohamed; Jaafar, Lahcen; Flores-Rozas, Hernan
Abstract:
DNA mismatch repair corrects mispaired bases and small insertions/deletions in DNA. In eukaryotes, the mismatch repair complex MSH2-MSH6 binds to mispairs with only slightly higher affinity than to fully paired DNA in vitro. Recently, the high-mobility group box1 protein, (HMGB1), has been shown to stimulate the mismatch repair reaction in vitro. In yeast, the closest homologs of HMGB1 are NHP6A and NHP6B. These proteins have been shown to be required for genome stability maintenance and mutagenesis control. In this work, we show that MSH2-MSH6 and NHP6A modulate their binding to DNA in vitro. Binding of the yeast MSH2-MSH6 to homoduplex regions of DNA significantly stimulates the loading of NHP6A. Upon binding of NHP6A to DNA, MSH2-MSH6 is excluded from binding unless a mismatch is present. A DNA binding-impaired MSH2-MSH6F337A significantly reduced the loading of NHP6A to DNA, suggesting that MSH2-MSH6 binding is a requisite for NHP6A loading. MSH2-MSH6 and NHP6A form a stable complex, which is responsive to ATP on mismatched substrates. These results suggest that MSH2-MSH6 binding to homoduplex regions of DNA recruits NHP6A, which then prevents further binding of MSH2-MSH6 to these sites unless a mismatch is present.
Citation:
Nucleic Acids Res. 2009 Dec; 37(22):7581-7589
Issue Date:
16-Dec-2009
URI:
http://hdl.handle.net/10675.2/69
DOI:
10.1093/nar/gkp649
PubMed ID:
19843605
PubMed Central ID:
PMC2794155
Type:
Journal Article
ISSN:
1362-4962
Appears in Collections:
Georgia Cancer Center: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorLabazi, Mohameden_US
dc.contributor.authorJaafar, Lahcenen_US
dc.contributor.authorFlores-Rozas, Hernanen_US
dc.date.accessioned2010-09-24T21:39:16Z-
dc.date.available2010-09-24T21:39:16Z-
dc.date.issued2009-12-16en_US
dc.identifier.citationNucleic Acids Res. 2009 Dec; 37(22):7581-7589en_US
dc.identifier.issn1362-4962en_US
dc.identifier.pmid19843605en_US
dc.identifier.doi10.1093/nar/gkp649en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/69-
dc.description.abstractDNA mismatch repair corrects mispaired bases and small insertions/deletions in DNA. In eukaryotes, the mismatch repair complex MSH2-MSH6 binds to mispairs with only slightly higher affinity than to fully paired DNA in vitro. Recently, the high-mobility group box1 protein, (HMGB1), has been shown to stimulate the mismatch repair reaction in vitro. In yeast, the closest homologs of HMGB1 are NHP6A and NHP6B. These proteins have been shown to be required for genome stability maintenance and mutagenesis control. In this work, we show that MSH2-MSH6 and NHP6A modulate their binding to DNA in vitro. Binding of the yeast MSH2-MSH6 to homoduplex regions of DNA significantly stimulates the loading of NHP6A. Upon binding of NHP6A to DNA, MSH2-MSH6 is excluded from binding unless a mismatch is present. A DNA binding-impaired MSH2-MSH6F337A significantly reduced the loading of NHP6A to DNA, suggesting that MSH2-MSH6 binding is a requisite for NHP6A loading. MSH2-MSH6 and NHP6A form a stable complex, which is responsive to ATP on mismatched substrates. These results suggest that MSH2-MSH6 binding to homoduplex regions of DNA recruits NHP6A, which then prevents further binding of MSH2-MSH6 to these sites unless a mismatch is present.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAdenosine Triphosphatases / metabolismen_US
dc.subject.meshAdenosine Triphosphate / metabolismen_US
dc.subject.meshBase Pair Mismatchen_US
dc.subject.meshDNA / metabolismen_US
dc.subject.meshDNA-Binding Proteins / metabolismen_US
dc.subject.meshHMGN Proteins / isolation & purification / metabolismen_US
dc.subject.meshMutS Homolog 2 Protein / metabolismen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshSaccharomyces cerevisiae Proteins / isolation & purification / metabolismen_US
dc.titleModulation of the DNA-binding activity of Saccharomyces cerevisiae MSH2-MSH6 complex by the high-mobility group protein NHP6A, in vitro.en_US
dc.typeJournal Articleen_US
dc.identifier.pmcidPMC2794155en_US
dc.contributor.corporatenameGHSU Cancer Centeren_US
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