# Regulating and Monitoring Meiotic Synapsis in C. elegans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $312,389

## Abstract

Project Summary
 Meiosis generates haploid gametes, such as sperm and eggs, from a diploid cell such that a diploid
genome is restored upon fertilization. The proper segregation of chromosomes during the meiotic divisions
relies on events in meiotic prophase, such as synapsis of homologous chromosomes and crossover
recombination. Errors in chromosome segregation are usually fatal to the fertilized zygote but can also result in
cancer predisposition or developmental disorders. In C. elegans, a meiotic checkpoint monitors homolog
synapsis, independent of a DNA damage/recombination checkpoint, and activates apoptosis to avoid the
generation of aneuploid gametes. This checkpoint depends on Pairing Centers (PCs), chromosome sites that
act as sites for synapsis initiation. PCs promote synapsis by nucleating structures at the nuclear envelope to
gain access to cytoplasmic microtubules and mobilize chromosomes. Since PCs mediate microtubule
attachment and are regulatory platforms for checkpoints that monitor chromosome behavior, PCs have been
compared to centromeres. Although the cytoskeletal-mediated mobilization of chromosomes is a common
feature of meiotic prophase, its specific function during synapsis is not well understood.
 Our initial studies of this meiotic checkpoint have revealed that the monitoring and regulation of homolog
synapsis are mechanistically linked: components of this checkpoint are also required to mediate synapsis. We
have also uncovered a surprising connection between the synapsis checkpoint and the mitotic spindle
checkpoint. Using a combination of genetic, biochemical and cytological approaches, we plan to further
investigate this link between synapsis initiation, synapsis checkpoint activation and PC function. We will
answer the following questions: 1) Do factors required for the synapsis checkpoint regulate PC movement to
inhibit synapsis initiation? 2) What functions of MAD-1 and MAD-2 are required to regulate and monitor
synapsis? 3) Does the conserved protein Shugoshin define a new pathway to regulate and monitor synapsis?
Given that the mobilization of chromosomes during meiotic prophase is conserved, it is likely that our studies
will provide important information about the regulation of synapsis even in systems that do not rely on PCs for
synapsis.

## Key facts

- **NIH application ID:** 9961606
- **Project number:** 5R01GM097144-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Needhi Bhalla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $312,389
- **Award type:** 5
- **Project period:** 2011-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961606

## Citation

> US National Institutes of Health, RePORTER application 9961606, Regulating and Monitoring Meiotic Synapsis in C. elegans (5R01GM097144-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9961606. Licensed CC0.

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