Coordinated and Independent Roles for MLH Subunits in DNA Repair

The MutL family of DNA mismatch repair proteins (MMR) acts to maintain genomic integrity in somatic and meiotic cells. In baker’s yeast, the MutL homolog (MLH) MMR proteins form three heterodimeric complexes, MLH1-PMS1, MLH1-MLH2, and MLH1-MLH3. The recent discovery of human PMS2 (homolog of baker’s...

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Main Authors: Gianno Pannafino, Eric Alani
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/4/948
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author Gianno Pannafino
Eric Alani
author_facet Gianno Pannafino
Eric Alani
author_sort Gianno Pannafino
collection DOAJ
description The MutL family of DNA mismatch repair proteins (MMR) acts to maintain genomic integrity in somatic and meiotic cells. In baker’s yeast, the MutL homolog (MLH) MMR proteins form three heterodimeric complexes, MLH1-PMS1, MLH1-MLH2, and MLH1-MLH3. The recent discovery of human PMS2 (homolog of baker’s yeast PMS1) and MLH3 acting independently of human MLH1 in the repair of somatic double-strand breaks questions the assumption that MLH1 is an obligate subunit for MLH function. Here we provide a summary of the canonical roles for MLH factors in DNA genomic maintenance and in meiotic crossover. We then present the phenotypes of cells lacking specific MLH subunits, particularly in meiotic recombination, and based on this analysis, propose a model for an independent early role for MLH3 in meiosis to promote the accurate segregation of homologous chromosomes in the meiosis I division.
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spelling doaj.art-b7fcd1e83f814b738c9624513ddfa93b2023-11-21T16:16:53ZengMDPI AGCells2073-44092021-04-0110494810.3390/cells10040948Coordinated and Independent Roles for MLH Subunits in DNA RepairGianno Pannafino0Eric Alani1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USADepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USAThe MutL family of DNA mismatch repair proteins (MMR) acts to maintain genomic integrity in somatic and meiotic cells. In baker’s yeast, the MutL homolog (MLH) MMR proteins form three heterodimeric complexes, MLH1-PMS1, MLH1-MLH2, and MLH1-MLH3. The recent discovery of human PMS2 (homolog of baker’s yeast PMS1) and MLH3 acting independently of human MLH1 in the repair of somatic double-strand breaks questions the assumption that MLH1 is an obligate subunit for MLH function. Here we provide a summary of the canonical roles for MLH factors in DNA genomic maintenance and in meiotic crossover. We then present the phenotypes of cells lacking specific MLH subunits, particularly in meiotic recombination, and based on this analysis, propose a model for an independent early role for MLH3 in meiosis to promote the accurate segregation of homologous chromosomes in the meiosis I division.https://www.mdpi.com/2073-4409/10/4/948MutL homologsMLHDNA mismatch repairmeiosisHolliday junction resolutionhomologous recombination
spellingShingle Gianno Pannafino
Eric Alani
Coordinated and Independent Roles for MLH Subunits in DNA Repair
Cells
MutL homologs
MLH
DNA mismatch repair
meiosis
Holliday junction resolution
homologous recombination
title Coordinated and Independent Roles for MLH Subunits in DNA Repair
title_full Coordinated and Independent Roles for MLH Subunits in DNA Repair
title_fullStr Coordinated and Independent Roles for MLH Subunits in DNA Repair
title_full_unstemmed Coordinated and Independent Roles for MLH Subunits in DNA Repair
title_short Coordinated and Independent Roles for MLH Subunits in DNA Repair
title_sort coordinated and independent roles for mlh subunits in dna repair
topic MutL homologs
MLH
DNA mismatch repair
meiosis
Holliday junction resolution
homologous recombination
url https://www.mdpi.com/2073-4409/10/4/948
work_keys_str_mv AT giannopannafino coordinatedandindependentrolesformlhsubunitsindnarepair
AT ericalani coordinatedandindependentrolesformlhsubunitsindnarepair