# Timing and regulation of meiotic commitment

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2021 · $305,297

## Abstract

Project Summary/Abstract:
 During meiosis, a diploid cell undergoes one round of replication followed by two rounds of
chromosome segregation to ultimately produce haploid gametes. A failure to properly segregate chromosomes
in meiosis can result in infertility, miscarriage, and trisomy conditions, such as Down syndrome. Despite the
importance of meiosis, there is a lack of molecular understanding of how cell-cycle regulatory networks
function to ensure that chromosomes properly attach to spindle microtubules in meiosis I and meiosis II. The
objective of this proposal is to determine the mechanisms of meiotic regulation that ensure proper chromosome
segregation in meiosis. These studies employ S. cerevisiae as the model organism due to the ease in
developing tools to address mechanistic questions. These innovative tools will allow the investigation of how
cells correct improper microtubule-kinetochore attachments, how cells set the duration of meiosis, and how
crossover position along homologous chromosomes affect microtubule-kinetochore attachments. The rationale
for the proposed research is that the questions were chosen to focus on processes that are likely to be highly
conserved, allowing the findings in budding yeast to uncover general mechanisms of meiotic regulation. Strong
preliminary data guided the following three specific aims: 1) Investigate how spindle checkpoint proteins
crosstalk with kinases and phosphatases at the kinetochore to regulate the timing and fidelity of chromosome
segregation in meiosis; 2) Determine how the spindle checkpoint is prematurely silenced during meiosis when
chromosomes are not correctly attached to spindle microtubules; and, 3) Determine how crossover location
along a chromosome can affect the fidelity of kinetochore-microtubule attachments. In the first aim, cell-cycle
regulators at the kinetochore will be tested for their role in maintaining the timing and accuracy of meiosis. The
second aim tests the novel hypothesis of a meiosis-specific mechanism for silencing the spindle checkpoint to
ensure the formation of gametes, even without proper chromosome segregation. The third aim addresses the
long unanswered question of why chromosomes with crossovers at sub-optimal positions are more likely to
mis-segregate. Strains will be developed that have chromosomes engineered to form a crossover at a specific
site and fast live cell imaging will monitor the attachment to microtubules. The innovative approach of
combining the latest imaging technologies to monitor kinetochore-microtubule attachments in engineered
strains allows the testing of novel hypotheses about cell-cycle regulation. The proposed research is significant
because the results are expected to reveal general principles of meiotic regulation important for protecting
genome integrity. Ultimately, the results will further our understanding of how errors in meiosis facilitate
developmental abnormalities.

## Key facts

- **NIH application ID:** 10115063
- **Project number:** 5R01GM105755-07
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Soni Lacefield
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $305,297
- **Award type:** 5
- **Project period:** 2014-08-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115063

## Citation

> US National Institutes of Health, RePORTER application 10115063, Timing and regulation of meiotic commitment (5R01GM105755-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115063. Licensed CC0.

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