# Centromere Interactions and Meiotic Chromosome Segregation in Yeast

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $349,600

## Abstract

Project Summary
 Homologous chromosomes enter meiosis unconnected to each other, but they become linked by
crossovers (exchanges). These linkages help the homologous chromosomes to move away from each other in
meiosis I. The linkages transmit tension between the homologous centromeres when they become attached to
microtubules from opposite sides of the spindle (bi-oriented). Tension stabilizes these microtubule
attachments. Accordingly, failures in crossing-over can result in meiotic errors and aneuploid gametes. The
pairing of homologous centromeres (CEN-pairing) in meiotic prophase, is a recently discovered, conserved
phenomenon. In yeast, CEN-pairing helps the partner chromosomes, later, in anaphase I, to segregate
properly, even if they have failed to experience a crossover. The mechanism by which CEN-pairing promotes
segregation is unknown. While crossover formation has been investigated for decades, very little is known
about how CEN-pairing promotes meiotic chromosome segregation. This is the focus of our proposal. In Aim
1 we test the hypothesis that the CEN-pairing allows the formation of centromere-centromere connections that
improve the segregation fidelity of meiotic chromosome partners. We will use live cell imaging to monitor the
meiotic behavior of chromosome pairs have or have not undergone CEN-pairing. In Aim 2 we will test the
hypothesis that connections formed during CEN-pairing are mediated by cohesin proteins. Aim 3 will explore
mechanism by which centromere-centromere connections help partner chromosomes become bi-oriented on
the spindle. We will directly measure the spring-like properties of the centromere-to-centromere connections
using bio-physical approaches and test whether partners with a centromere-centromere connection can use
the tension-sensing signaling pathways. In addition, these experiments will test the hypothesis that
centromere-centromere connections are important to improve the segregation fidelity of chromosome pairs
linked by crossovers that alone would be ineffective in creating a tension-transmitting bridge as the pair
attaches to microtubules. Together, the experiments in this project will elucidate the reasons that some
crossovers do, and some don’t, effectively ensure high fidelity chromosome segregation in meiosis and will
explain how the recently described process of centromere pairing can mediate the formation of a centromere-
to-centromere connection between homologs that augments the functionality of crossovers, or can act alone
when crossovers fail.

## Key facts

- **NIH application ID:** 10210732
- **Project number:** 1R01GM138889-01A1
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** DEAN S DAWSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $349,600
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210732

## Citation

> US National Institutes of Health, RePORTER application 10210732, Centromere Interactions and Meiotic Chromosome Segregation in Yeast (1R01GM138889-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10210732. Licensed CC0.

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