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Updated: Dec 15, 2025
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Published on: June 26, 2020
Expanded roles for the MutL family of DNA mismatch repair proteins
Christopher M Furman1, Ryan Elbashir1, Eric Alani1
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
Abstract:
The MutL family of DNA mismatch repair proteins plays a critical role in excising and repairing misincorporation errors during DNA replication. In many eukaryotes, members of this family have evolved to modulate and resolve recombination intermediates into crossovers during meiosis. In these organisms, such functions promote the accurate segregation of chromosomes during the meiosis I division. What alterations occurred in MutL homolog (MLH) family members that enabled them to acquire these new roles? In this review, we present evidence that the yeast Mlh1-Mlh3 and Mlh1-Mlh2 complexes have evolved novel enzymatic and nonenzymatic activities and protein-protein interactions that are critical for their meiotic functions. Curiously, even with these changes, these complexes retain backup and accessory roles in DNA mismatch repair during vegetative growth.
Insights
The MutL homolog (MLH) family proteins evolved new roles in meiosis for accurate chromosome segregation. These MLH complexes retain DNA mismatch repair functions during vegetative growth.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA mismatch repair (MMR) proteins, including the MutL family, correct replication errors.
- In eukaryotes, MutL homologs (MLH) also regulate meiotic recombination and chromosome segregation.
- Understanding MLH evolution is key to comprehending meiotic fidelity.
Purpose of the Study:
- To investigate the evolutionary alterations in MLH family members that enabled their meiotic functions.
- To elucidate the novel activities and interactions of yeast Mlh1-Mlh3 and Mlh1-Mlh2 complexes in meiosis.
Main Methods:
- Review of existing literature on MLH protein functions.
- Analysis of enzymatic and nonenzymatic activities.
- Examination of protein-protein interactions.
Main Results:
- Yeast Mlh1-Mlh3 and Mlh1-Mlh2 complexes exhibit evolved enzymatic and nonenzymatic activities crucial for meiotic functions.
- These complexes are vital for resolving recombination intermediates into crossovers.
- MLH complexes maintain essential DNA mismatch repair roles during vegetative growth.
Conclusions:
- MLH family proteins have acquired specialized meiotic roles through evolutionary adaptations.
- These adaptations enhance chromosome segregation accuracy during meiosis I.
- Dual functionality of MLH complexes in both meiosis and DNA repair is conserved.
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