# Novel mechanisms in DNA mismatch repair

> **NIH NIH R01** · SOUTHERN ILLINOIS UNIVERSITY CARBONDALE · 2021 · $292,544

## Abstract

Project summary: The mismatch repair system is a major DNA repair system that has been conserved from
bacteria to humans. It maintains genome stability by removing DNA replication errors, preventing homeologous
recombination, and participating in the cytotoxic response to irreparable DNA damage. Genome stability
provided by the mismatch repair system protects humans from both sporadic and inherited cancers. Although
mismatch repair is error-free in the majority of genomic sites, it is error-prone at certain genomic loci. Mutations
formed by error-prone mismatch repair have both beneficial and detrimental consequences for human health.
All functions of the mismatch repair system depend on its ability to process DNA mismatches. The initial step in
processing of mismatch-containing DNA by the eukaryotic mismatch repair system is recognition of the
mismatch by MutSα or MutSβ. The steps that occur downstream from the mismatch recognition step are not
well understood. Recent progress in the field has revealed a eukaryotic mismatch repair mechanism that relies
on the 5′→3′ exonuclease activity of Exo1. However, significant genetic, epidemiological, and biochemical
evidence has suggested that the Exo1-dependent mechanism is not the only mechanism in eukaryotic
mismatch repair. During our preliminary studies we have discovered that there are novel mechanisms in
eukaryotic mismatch repair. The goal of this project is to define these novel mechanisms in the yeast S.
cerevisiae and human cells. The proposed studies will take advantage of our unique expertise in the mismatch
repair field and will utilize a diverse array of genetic and biochemical approaches, fluorescence microscopy of
live cells, and next generation sequencing. The results will provide novel insights into the mechanisms in
mismatch repair and will help to develop innovative approaches to prevent and treat human diseases caused
by defects in mismatch repair.

## Key facts

- **NIH application ID:** 10244954
- **Project number:** 5R01GM132128-02
- **Recipient organization:** SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
- **Principal Investigator:** Farid Kadyrov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $292,544
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244954

## Citation

> US National Institutes of Health, RePORTER application 10244954, Novel mechanisms in DNA mismatch repair (5R01GM132128-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10244954. Licensed CC0.

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