TY - JOUR
T1 - Functional specificity of MutL homologs in yeast
T2 - Evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction
AU - Wang, Ting Fang
AU - Kleckner, Nancy
AU - Hunter, Neil
PY - 1999/11/23
Y1 - 1999/11/23
N2 - The yeast genome encodes four proteins (Pms1 and Mlh1-3) homologous to the bacterial mismatch repair component, MutL. Using two hybrid-interaction and coimmunoprecipitation studies, we show that these proteins can form only three types of complexes in vivo. Mlh1 is the common component of all three complexes, interacting with Pms1, Mlh2, and Mlh3, presumptively as heterodimers. The phenotypes of single deletion mutants reveal distinct functions for the three heterodimers during meiosis: in a pms1 mutant, frequent postmeiotic segregation indicates a defect in the correction of heteroduplex DNA, whereas the frequency of crossing-over is normal. Conversely, crossing-over in the mlh3 mutant is reduced to ≃70% of wild-type levels but correction of heteroduplex is normal. In a mlh2 mutant, crossing- over is normal and postmeiotic segregation is not observed but non-Mendelian segregation is elevated and altered with respect to parity. Finally, to a first approximation, the mlh1 mutant represents the combined single mutant phenotypes. Taken together, these data imply modulation of a basic Mlh1 function via combination with the three other MutL homologs and suggest specifically that Mlh1 combines with Mlh3 to promote meiotic crossing-over.
AB - The yeast genome encodes four proteins (Pms1 and Mlh1-3) homologous to the bacterial mismatch repair component, MutL. Using two hybrid-interaction and coimmunoprecipitation studies, we show that these proteins can form only three types of complexes in vivo. Mlh1 is the common component of all three complexes, interacting with Pms1, Mlh2, and Mlh3, presumptively as heterodimers. The phenotypes of single deletion mutants reveal distinct functions for the three heterodimers during meiosis: in a pms1 mutant, frequent postmeiotic segregation indicates a defect in the correction of heteroduplex DNA, whereas the frequency of crossing-over is normal. Conversely, crossing-over in the mlh3 mutant is reduced to ≃70% of wild-type levels but correction of heteroduplex is normal. In a mlh2 mutant, crossing- over is normal and postmeiotic segregation is not observed but non-Mendelian segregation is elevated and altered with respect to parity. Finally, to a first approximation, the mlh1 mutant represents the combined single mutant phenotypes. Taken together, these data imply modulation of a basic Mlh1 function via combination with the three other MutL homologs and suggest specifically that Mlh1 combines with Mlh3 to promote meiotic crossing-over.
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U2 - 10.1073/pnas.96.24.13914
DO - 10.1073/pnas.96.24.13914
M3 - Article
C2 - 10570173
AN - SCOPUS:0033598817
VL - 96
SP - 13914
EP - 13919
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 24
ER -