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The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations

H Flores-Rozas1, R D Kolodner

  • 1Ludwig Institute for Cancer Research, Cancer Center and Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 15, 1998
PubMed

Insights

The study reveals that MLH3 plays a role in DNA mismatch repair, particularly in correcting small insertion-deletion errors. It works with MLH1 to form a complex that aids in repairing specific DNA mismatches.

Area of Science:

  • Molecular Biology
  • Genetics
  • DNA Repair Mechanisms

Background:

  • The Saccharomyces cerevisiae genome has four MutL homologs.
  • MLH1 and PMS1 are established components of the MSH2-dependent DNA mismatch repair pathway.
  • The specific role of MLH3 in mismatch repair remained largely uncharacterized.

Purpose of the Study:

  • To investigate the function of MLH3 in DNA mismatch repair.
  • To determine the interaction of MLH3 with other mismatch repair proteins.
  • To elucidate the specific types of DNA mismatches repaired by MLH3-containing complexes.

Main Methods:

  • Analysis of reversion rates for specific alleles (hom3-10) in yeast mutants.
  • Assessment of mutation accumulation at frameshift hotspots in the LYS2 gene.
  • Yeast two-hybrid system to study protein-protein interactions.

Main Results:

  • MLH3 mutations increased the rate of single T deletions in a homopolymeric tract.
  • Synergistic increase in reversion rates observed in mlh3 msh6 double mutants.
  • MLH3 interacts with MLH1, suggesting a functional complex.

Conclusions:

  • MLH3 is involved in repairing specific insertion/deletion mismatches.
  • A heterodimeric MLH1-MLH3 complex likely participates in MSH3-dependent mismatch repair.
  • This MLH1-MLH3 complex may function in parallel to the MLH1-PMS1 complex.

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