Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, the essential mismatch repair (MMR) endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had...
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doaj-495a2c90b0c046fe8c47ec0ea2fa39792020-11-25T02:23:07ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-05-01105e100432710.1371/journal.pgen.1004327Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae.Christopher S CampbellHans HombauerAnjana SrivatsanNikki BowenKerstin GriesArshad DesaiChristopher D PutnamRichard D KolodnerIn Saccharomyces cerevisiae, the essential mismatch repair (MMR) endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had a longer lifetime than Mlh1-Pms1 foci. Mlh1-Mlh2 foci were similar to Mlh1-Pms1 foci: they required mispair recognition by Msh2-Msh6, increased in response to increased mispairs or downstream defects in MMR, and formed after induction of DNA damage by phleomycin but not double-stranded breaks by I-SceI. Mlh1-Mlh2 could be recruited to mispair-containing DNA in vitro by either Msh2-Msh6 or Msh2-Msh3. Deletion of MLH2 caused a synergistic increase in mutation rate in combination with deletion of MSH6 or reduced expression of Pms1. Phylogenetic analysis demonstrated that the S. cerevisiae Mlh2 protein and the mammalian PMS1 protein are homologs. These results support a hypothesis that Mlh1-Mlh2 is a non-essential accessory factor that acts to enhance the activity of Mlh1-Pms1.http://europepmc.org/articles/PMC4014439?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christopher S Campbell Hans Hombauer Anjana Srivatsan Nikki Bowen Kerstin Gries Arshad Desai Christopher D Putnam Richard D Kolodner |
spellingShingle |
Christopher S Campbell Hans Hombauer Anjana Srivatsan Nikki Bowen Kerstin Gries Arshad Desai Christopher D Putnam Richard D Kolodner Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae. PLoS Genetics |
author_facet |
Christopher S Campbell Hans Hombauer Anjana Srivatsan Nikki Bowen Kerstin Gries Arshad Desai Christopher D Putnam Richard D Kolodner |
author_sort |
Christopher S Campbell |
title |
Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae. |
title_short |
Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae. |
title_full |
Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae. |
title_fullStr |
Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae. |
title_full_unstemmed |
Mlh2 is an accessory factor for DNA mismatch repair in Saccharomyces cerevisiae. |
title_sort |
mlh2 is an accessory factor for dna mismatch repair in saccharomyces cerevisiae. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2014-05-01 |
description |
In Saccharomyces cerevisiae, the essential mismatch repair (MMR) endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had a longer lifetime than Mlh1-Pms1 foci. Mlh1-Mlh2 foci were similar to Mlh1-Pms1 foci: they required mispair recognition by Msh2-Msh6, increased in response to increased mispairs or downstream defects in MMR, and formed after induction of DNA damage by phleomycin but not double-stranded breaks by I-SceI. Mlh1-Mlh2 could be recruited to mispair-containing DNA in vitro by either Msh2-Msh6 or Msh2-Msh3. Deletion of MLH2 caused a synergistic increase in mutation rate in combination with deletion of MSH6 or reduced expression of Pms1. Phylogenetic analysis demonstrated that the S. cerevisiae Mlh2 protein and the mammalian PMS1 protein are homologs. These results support a hypothesis that Mlh1-Mlh2 is a non-essential accessory factor that acts to enhance the activity of Mlh1-Pms1. |
url |
http://europepmc.org/articles/PMC4014439?pdf=render |
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