# Recombination pathway and partner choices during meiosis

> **NIH NIH R35** · UNIVERSITY OF OREGON · 2022 · $36,875

## Abstract

Research Summary
Recombination between chromosomes is required to generate genetic variation, maintain genome integrity
through the repair of double strand DNA breaks (DSBs), and ensure proper chromosome segregation during
meiosis, the specialized cell division program by which diploid organisms generate haploid gametes such as
sperm and eggs. Perturbations in recombination can compromise these basic cellular functions, ultimately
leading to cancer, infertility, or birth defects. Meiotic recombination is initiated by DSBs, which are repaired
using meiosis-specific mechanisms that favor utilization of the homologous chromosome (instead of the sister
chromatid) as the recombination partner and that promote a crossover outcome of the DSB repair process,
which is required for promoting proper chromosome segregation during meiosis. Although repair of DSBs with
the appropriate template (homologous chromosome) is necessary for proper chromosome segregation and
genome integrity, our knowledge about how germ cells achieve this template preference in the presence of
nearly identical sequences (sister chromatids) is limited. The goal of our research program is to understand
how chromosomes are able to access distinct recombination pathways and partners depending on the
chromosomal and cellular context to ensure faithful genome inheritance. Using Caenorhabditis elegans as a
model system, we have developed an assay to monitor repair of an induced DSB with the sister chromatid
during meiotic prophase progression in vivo. We now have evidence for the presence of a switch in repair
partner preferences from the homologous chromosome to the sister chromatid during late meiotic prophase. In
this proposal we will begin to lay the foundation for understanding how specific DSB repair pathways and
partners are engaged and regulated during meiosis. To determine how these different repair partner choices
are regulated, we will identify the molecular signatures, chromosomal features, and proteins associated with
these different repair outcomes. Further, we will use live imaging, a new live genomic locus tracking system,
and genetics to determine the how early DSB repair dynamics influence DSB repair outcomes. Further, we will
use superresolution and high-resolution microscopy methods to assess the effects of DSB repair on meiotic
chromosome structures and DNA organization. Overall, these studies will reveal how recombination pathway
and partner choices ensure that chromosomes form the connections necessary for chromosome segregation
and repair DSBs for maintaining genomic integrity during sperm and egg development.

## Key facts

- **NIH application ID:** 10569375
- **Project number:** 3R35GM128890-04S1
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Diana Elizabeth Libuda
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $36,875
- **Award type:** 3
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10569375

## Citation

> US National Institutes of Health, RePORTER application 10569375, Recombination pathway and partner choices during meiosis (3R35GM128890-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10569375. Licensed CC0.

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