# Uncovering the Role of Exo1 in Meiotic Recombination

> **NIH NIH F31** · CORNELL UNIVERSITY · 2024 · $20,231

## Abstract

PROJECT SUMMARY
Meiosis is a specialized form of cell division that results in the formation of gametes. Meiotic recombination is a
crucial step in this process during which homologous chromosomes physically interact and exchange genetic
information. The final recombination DNA intermediate in this process is the double Holliday Junction (dHJ). A
major question in the meiosis field is the mechanism through which dHJs are resolved in a biased manner to
create crossover products between homologs. Mlh1-Mlh3, the nuclease responsible for resolving the majority
of dHJs in budding yeast, does not appear to be intrinsically capable of recognizing and cleaving dHJs in a
biased manner. This observation combined with genetic screens revealing a wide variety of crossover
promoting factors indicates that other proteins may interact at the dHJ to promote biased resolution. Here I aim
to interrogate Exo1, a crossover promoting factor with well-established roles as a nuclease in homology
directed repair (HDR) and mismatch repair (MMR). Interestingly, despite playing an important role in crossover
formation previous work shows that catalytically deficient exo1 mutants do not suffer reductions in crossover
frequencies, suggesting a meiotic role for Exo1 that is independent of its nuclease activity. Here, I will
investigate the mechanism through which Exo1 promotes the formation of crossovers. I hypothesize that Exo1
acts as a scaffold at the dHJ to stabilize and orient Mlh1-Mlh3 through direct interaction with both the DNA and
Mlh1. Additionally, I will follow up on my recent work indicating a pro-CO activity of Exo1 independent of Mlh1
Mlh3 functions that acts upstream of resolution. This work will provide insight into long-standing questions in
the meiosis field and open up exciting new paths for future research.

## Key facts

- **NIH application ID:** 10765636
- **Project number:** 5F31GM145163-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Lisette Payero
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $20,231
- **Award type:** 5
- **Project period:** 2022-01-06 → 2024-07-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765636

## Citation

> US National Institutes of Health, RePORTER application 10765636, Uncovering the Role of Exo1 in Meiotic Recombination (5F31GM145163-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10765636. Licensed CC0.

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