# Synaptonemal complex assembly and function in meiosis

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2021 · $62,420

## Abstract

PROJECT SUMMARY
Failure to achieve accurate chromosome segregation during meiosis is a leading cause of
miscarriages, infertility, and birth defects such as Down syndrome. Therefore, understanding the
mechanisms underlying accurate chromosome segregation during meiosis is of paramount
importance to human health. The synaptonemal complex (SC) is a zipper-like structure
ubiquitously present during meiosis from yeast to humans where it assembles between
homologous chromosomes stabilizing homologous pairing interactions and promoting
interhomolog crossover formation. However, despite its importance for key events required for
accurate chromosome segregation during meiosis, the mechanisms regulating chromosome
synapsis are not well understood in any organism. Moreover, studies focused on the post-
translational regulation of proteins forming this structure are uncovering novel roles for the SC,
linking it to the regulation of DSB formation and crossover designation. These recent findings
further underscore the importance of this structure and of uncovering the roles it plays during
meiosis. Our goal is to address these critical issues by taking advantage of the ease of genetic,
cytological, molecular and biochemical analysis that is afforded by the use of the nematode C.
elegans, an ideal model system for germline studies. Our progress during the previous funding
period, coupled with new data and molecular targets, place us in an ideal position to understand
the regulation of chromosome synapsis and the roles exerted by the SC during meiosis. Here
we propose two integrated aims to address these critical issues. Aim 1 will address how
ATM/ATR-mediated phosphorylation of SYP-4, a central region component of the SC, regulates
SC dynamics, DNA double-strand break (DSB) repair, and crossover frequency and distribution.
Aim 2 will determine the mechanisms of function for GRAS-1, a new and conserved protein of
previously unknown meiotic function, which our studies implicate in regulating SC assembly and
we hypothesize may act as a molecular scaffold for structural components of the SC. We will
also investigate the functional conservation shared between GRAS-1 and mammalian GRASP
and CYTIP proteins, through combined studies in C. elegans and mice. These studies will shed
new light on our understanding of the mechanisms regulating chromosome synapsis and the
roles of the SC. Our studies are expected to impact multiple fields of tremendous relevance to
human health including chromosome dynamics, the study of post-translational modifications,
and regulation of macromolecular structures. Taken together, this application will provide
significant new insights into the molecular mechanisms regulating accurate chromosome
segregation during meiosis.

## Key facts

- **NIH application ID:** 10409402
- **Project number:** 3R01GM072551-16S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Monica P Colaiacovo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $62,420
- **Award type:** 3
- **Project period:** 2005-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409402

## Citation

> US National Institutes of Health, RePORTER application 10409402, Synaptonemal complex assembly and function in meiosis (3R01GM072551-16S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10409402. Licensed CC0.

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