# Synaptonemal Complex Assembly and Function in Meiosis

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2024 · $448,683

## 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 meiotic chromosome segregation is of paramount importance to human health. The synaptonemal
complex (SC) is a zipper-like structure present from yeast to humans during meiosis that assembles between
homologous chromosomes, stabilizing homologous pairing interactions and promoting interhomolog crossover
formation. However, despite its importance for achieving accurate meiotic chromosome segregation, the
mechanisms regulating chromosome synapsis and how the SC interfaces with recombination and chromosome
remodeling is not well understood in any organism. Our goal is to identify mechanisms regulating the SC and to
determine how SC regulation is linked to DNA double-strand break (DSB) repair progression and late prophase
I chromosome remodeling to ensure accurate meiotic chromosome segregation. We study this in the nematode
C. elegans because it shares a high degree of gene conservation with humans and affords ease of genetic,
cytological, molecular, and biochemical analysis 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
and roles of chromosome synapsis during meiosis. Here we propose two integrated aims to address these critical
issues. Aim 1 will determine how HIM-22, a protein which shares sequence conservation with yeast Set3 and
human ASH1L, regulates SC formation. HIM-22 promotes protein deacetylation in the germline, interacts with a
structural component of the SC, and is required for regulating SC assembly, crossover levels, and late prophase
I chromosome remodeling; this will define a previously unknown meiotic role for this protein modifier in a
metazoan and a new mode of SC regulation. Aim 2 will determine how NatF-mediated N-terminal acetylation of
meiotic proteins regulates the SC. Our studies show that NatF is required for protein acetylation in the germline,
and regulates SC assembly/disassembly, DSB repair progression, crossover distribution, and late prophase I
chromosome remodeling. We previously found that NatB-mediated N-terminal acetylation of a structural
component of the SC promotes SC assembly. Our past studies on NatB and our current discovery of NatF as a
potential regulator of the SC suggest there is a conserved yet poorly understood regulatory network of different
N-acetyltransferases acting on chromosome synapsis. These studies will shed new light on our understanding
of the mechanisms regulating chromosome synapsis and how these link the SC to DSB repair and late prophase
I chromosome remodeling. Our studies will impact multiple fields of tremendous relevance to human health
including chromosome dynamics, the study of post-translational modifications, and regulation o...

## Key facts

- **NIH application ID:** 10801561
- **Project number:** 2R01GM072551-18A1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Monica P Colaiacovo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $448,683
- **Award type:** 2
- **Project period:** 2005-08-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801561

## Citation

> US National Institutes of Health, RePORTER application 10801561, Synaptonemal Complex Assembly and Function in Meiosis (2R01GM072551-18A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10801561. Licensed CC0.

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