# Synaptonemal complex assembly and function in meiosis

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2021 · $399,167

## 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:** 10220045
- **Project number:** 5R01GM072551-16
- **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:** $399,167
- **Award type:** 5
- **Project period:** 2005-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220045

## Citation

> US National Institutes of Health, RePORTER application 10220045, Synaptonemal complex assembly and function in meiosis (5R01GM072551-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220045. Licensed CC0.

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