# Recombination pathway and partner choices during meiosis

> **NIH NIH R35** · UNIVERSITY OF OREGON · 2024 · $471,376

## Abstract

RESEARCH SUMMARY
Recombination between chromosomes is required to generate genetic variation, maintain genome integrity,
and ensure proper chromosome segregation during meiosis, the specialized cell division program that
generates 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 programmed double strand DNA breaks (DSBs), which are repaired using meiosis-specific
mechanisms that 1) favor utilization of the homologous chromosome (instead of the sister chromatid) as the
repair partner; and, 2) promote a crossover outcome of the DSB repair process, which is required for 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 of how
germ cells achieve this critical template preference in the presence of nearly identical sequences (sister
chromatids) is limited due to assay limitations in metazoans. The goal of our research program is to
understand how chromosomes are able to access distinct recombination pathways and partners to ensure
faithful genome inheritance. Using in vivo assays we developed in the model system Caenorhabditis elegans,
we have directly detected and analyzed use of the sister chromatid as a repair template during metazoan
meiotic prophase I progression. Building upon our published work, we are defining and establishing how
specific chromosome structures, proteins, and cellular contexts regulate recombination pathway and repair
partner choices to maintain meiotic genome integrity. Using our in vivo assay along with a combination of
genetic, cytological, and sequencing based approaches, we will test models of how particular meiotic
chromosome structures regulate and respond to specific repair pathway and partner choices. We will also
determine how the NSE-2/Mms21 E3 SUMO ligase regulates repair pathway choices and genomic stability
during oogenesis. Using whole genome sequencing, we will define recombination landscape with its molecular
signatures to determine how chromosomal context, sex, and age affect crossover and noncrossover numbers
and distribution across the genome. Finally, we will induce and analyze single DSBs in specific genomic
locations to determine how specific chromosome features affect what pathways and partners are used to repair
a DSB. 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:** 10765522
- **Project number:** 2R35GM128890-06
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Diana Elizabeth Libuda
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $471,376
- **Award type:** 2
- **Project period:** 2018-08-15 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765522

## Citation

> US National Institutes of Health, RePORTER application 10765522, Recombination pathway and partner choices during meiosis (2R35GM128890-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10765522. Licensed CC0.

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