# Characterization of a Meiotic Crossover Surveillance System

> **NIH NIH R01** · MAGEE-WOMEN'S RES INST AND FOUNDATION · 2021 · $278,339

## Abstract

PROJECT SUMMARY
During the formation of egg and sperm, the maternally- and paternally-inherited chromosomes exchange
genetic material in the process known as meiotic crossover recombination. Crossing over creates a transient,
physical connection between the homologs that helps them align at metaphase and segregate to opposite
poles. Without crossing over, homologs segregate randomly which can lead to aneuploidy, a condition
associated with birth defects and miscarriage. The importance of crossover formation is underscored by the
extensive crosstalk between meiotic events that ensures their timely and orderly completion. We recently
identified a chromosome-by-chromosome surveillance system that couples crossover formation to timely
meiotic progression and to stabilization of the synaptonemal complex (SC), a molecular scaffold that stably
juxtaposes homologous chromosomes. The first crossover intermediate activates a systemic signal that both
changes the dynamics of the SC on the other chromosomes, making them meta-stable, and also promotes
chromosome mobility to potentiate crossover formation. We identified the nuclear membrane protein SUN-1
and the polo-like kinase, PLK-2, as key effectors of these signals. The current proposal expands our
characterization of the surveillance system to provide mechanistic insight into these processes. Genetic
screens will be used to identify the crossover intermediates that are recognized by the surveillance system and
the signaling molecules that communicate this to the progression machinery and SC. Using a combination of
biochemical and advanced microscopic approaches, we will dissect out the changes that occur to the SC upon
activation of the surveillance system and how this regulates crossover formation. We will also further delineate
the roles of SUN-1 and PLK-2 in the surveillance system. These studies will increase our understanding of
cellular mechanisms that promote genome stability through the monitoring of crossover intermediates. These
studies can provide insight into the etiology of birth defects, recurrent miscarriage, premature ovarian failure
and male infertility, opening avenues for diagnosis and therapeutic intervention.

## Key facts

- **NIH application ID:** 10219811
- **Project number:** 5R01GM104007-09
- **Recipient organization:** MAGEE-WOMEN'S RES INST AND FOUNDATION
- **Principal Investigator:** JUDITH YANOWITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $278,339
- **Award type:** 5
- **Project period:** 2013-03-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219811

## Citation

> US National Institutes of Health, RePORTER application 10219811, Characterization of a Meiotic Crossover Surveillance System (5R01GM104007-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219811. Licensed CC0.

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