# Sex-specific regulation of meiosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $305,048

## Abstract

Meiosis is a specialized form of cell division that leads to the production of two distinct gamete types, sperm
and egg, for sexual reproduction. In addition to a haploid set of chromosomes, sperm and egg must provide
the embryo with unique but complementary products to support development. To accomplish this, the meiotic
program is sexual dimorphic; however, the mechanisms underlying differences in male and female meiosis
have remained elusive. We have identified sex-specific roles for the tumor suppressor E3 ubiquitin ligase
BRCA1/BARD1 complex in meiotic recombination, and in checkpoint signaling, and thus are uniquely
positioned to determine the underlying molecular mechanisms regulating meiosis in the sexes. Our overall
hypothesis is that sex-specific differences in recombination and checkpoint signaling serve to balance
the accurate transmission of the genome with overall reproductive success. To test this hypothesis, we
propose to elucidate conserved mechanisms underlying chromosome behavior during male and female
meiosis using the simple metazoan animal model Caenorhabditis elegans, which overcomes many technical
challenges inherent in mammalian systems. In Aim 1 we will determine mechanistically how BRCA1/BARD1
mediates double-strand break processing in male versus female germ cells, using targeted genetic, cell
biological and biochemical approaches. We will also determine the significance of E3 ubiquitin ligase activity to
BRCA1/BARD1 function in meiosis. In Aim 2 we will elucidate mechanisms underlying how BRCA1/BARD1 is
regulated to perform the sex-specific functions defined in Aim 1. In Aim 3 we will uncover the role of
BRCA1/BARD1 in checkpoint signaling under conditions where there are errors in recombination and
chromosome alignment to determine mechanisms underlying the fidelity of male meiosis. Together, an
understanding of these processes in the genetically tractable C. elegans system will provide novel and
important insights into how the meiotic program is regulated in a sex-specific manner. These studies have
direct relevance to understanding the increased frequency of errors associated with human meiosis resulting in
developmental disorders such as Down’s Syndrome. Importantly, these studies will also elucidate general
mechanisms of, and the involvement of BRCA1/BARD1 in, DNA repair, chromosome segregation and
checkpoint signaling, events that play critical roles in maintaining genome integrity in all cells.

## Key facts

- **NIH application ID:** 10135102
- **Project number:** 5R01GM103860-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JOANNE ENGEBRECHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $305,048
- **Award type:** 5
- **Project period:** 2013-08-05 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135102

## Citation

> US National Institutes of Health, RePORTER application 10135102, Sex-specific regulation of meiosis (5R01GM103860-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10135102. Licensed CC0.

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