Reference: Flores-Rozas H and Kolodner RD (1998) The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Proc Natl Acad Sci U S A 95(21):12404-9

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Abstract


The Saccharomyces cerevisiae genome encodes four MutL homologs. Of these, MLH1 and PMS1 are known to act in the MSH2-dependent pathway that repairs DNA mismatches. We have investigated the role of MLH3 in mismatch repair. Mutations in MLH3 increased the rate of reversion of the hom3-10 allele by increasing the rate of deletion of a single T in a run of 7 Ts. Combination of mutations in MLH3 and MSH6 caused a synergistic increase in the hom3-10 reversion rate, whereas the hom3-10 reversion rate in an mlh3 msh3 double mutant was the same as in the respective single mutants. Similar results were observed when the accumulation of mutations at frameshift hot spots in the LYS2 gene was analyzed, although mutation of MLH3 did not cause the same extent of affect at every LYS2 frameshift hot spot. MLH3 interacted with MLH1 in a two-hybrid system. These data are consistent with the idea that a proportion of the repair of specific insertion/deletion mispairs by the MSH3-dependent mismatch repair pathway uses a heterodimeric MLH1-MLH3 complex in place of the MLH1-PMS1 complex.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S.
Authors
Flores-Rozas H, Kolodner RD
Primary Lit For
LYS2 | MLH3 | MSH3 | MSH6 | MLH1 | MLH2 | MLH1-MLH3 endonuclease complex
Additional Lit For
HOM3 | MSH2 | PMS1

Gene Ontology Annotations 3 entries for 2 genes


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Gene/ComplexQualifierGene Ontology TermAnnotation ExtensionEvidenceSourceAssigned On
MLH1part ofMutLgamma complexIPI with MLH3SGD2014-03-11
MLH3part ofMutLgamma complexIPI with MLH1SGD2014-03-11
MLH3involved inmismatch repairIMPSGD2013-08-07
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Interaction Annotations


Genetic Interactions

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Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions 1 entry for 2 genes

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InteractorInteractorAssayAnnotationActionModification
MLH1MLH3Two-hybridmanually curatedHit-BaitNo Modification
Showing 1 to 1 of 1 entries