# The molecular basis for the beneficial and deleterious functions of human MLH1-MLH3 complex

> **NIH NIH R03** · SOUTHERN ILLINOIS UNIVERSITY CARBONDALE · 2020 · $73,750

## Abstract

Project summary:
Homologous recombination that takes place in prophase of meiosis I is required for reproduction in humans
and other eukaryotes. Defects in meiotic homologous recombination in humans cause infertility, miscarriages,
and Down and Turner syndromes. The human MLH1-MLH3 complex (MutLγ) has been implicated in meiotic
homologous recombination, but its function in this process has not been defined. In addition to having a key
function in meiotic homologous recombination human MutLγ has other functions that are poorly understood.
One of these functions is required for triplet repeat DNA expansion, a process that causes several
neurodegenerative diseases. A lack of information about the action of MutLγ in meiotic recombination and
triplet repeat DNA expansion is a major gap in our understanding of these key biological processes. Our
preliminary data support the hypothesis that human MutLγ functions as an ATP-dependent endonuclease in
meiotic recombination and triplet repeat DNA expansion. The goal of this project is to investigate MutLγ and its
potential interactors and establish functional assays for future studies of MutLγ and MutLγ-dependent
mechanisms. In Aim 1, we will study endonuclease and ATPase activities of MutLγ in assays that will produce
novel insights into the functions of MutLγ in meiotic homologous recombination and triplet repeat instability. In
Aim 2, we will identify proteins that interact with human MutLγ. The results of the proposed research will
advance our understanding of MutLγ and will permit new studies into the mechanisms of MutLγ-dependent
meiotic recombination and triplet repeat DNA expansion.

## Key facts

- **NIH application ID:** 9893399
- **Project number:** 1R03HD098293-01A1
- **Recipient organization:** SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
- **Principal Investigator:** Farid Kadyrov
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $73,750
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893399

## Citation

> US National Institutes of Health, RePORTER application 9893399, The molecular basis for the beneficial and deleterious functions of human MLH1-MLH3 complex (1R03HD098293-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9893399. Licensed CC0.

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