# Analyis of meiotic chromosome synapsis in yeast

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $460,646

## Abstract

PROJECT SUMMARY
 Sexual reproduction requires the creation of haploid gametes from diploid cells. This
two-fold reduction in chromosome number is carried out by a specialized, evolutionarily
conserved, cell division called meiosis. In humans, failures in meiosis result in infertility and birth
defects such as Trisomy 21 or Down syndrome. Unique to meiosis is the first meiotic division,
in which homologous pairs of sister chromatids segregate to opposite poles. To promote proper
orientation at Metaphase I of meiosis, homologous chromosomes are physically connected by a
combination of sister chromatid cohesion and reciprocal crossovers. Crossovers result from
meiotic recombination, which is initiated by double strand breaks (DSBs). Repair of these DSBs
brings homologs together to form a structure called the synaptonemal complex (SC). Meiotic
DSB repair is highly regulated to ensure that each homolog pair gets at least one crossover and
that chromosome segregation is delayed until all DSBs have been repaired. An important
element of this regulation in budding yeast involves phosphorylation by the meiosis-specific
kinase, Mek1, as well as the conserved cell cycle kinases, CDK (cyclin-dependent kinase), DDK
(Cdc7-Dbf4) and polo-like kinase (Cdc5). The goal of this grant is to understand how
phosphorylation regulates meiotic recombination and chromosome synapsis.
 The first aim tests a specific mechanistic hypothesis for how meiotic DSB repair is
coordinated with meiotic progression through Mek1 phosphorylation of the meiosis-specific
transcription factor, Ndt80. The second aim addresses the role that phosphorylation of a
conserved region of an SC protein called Zip1 plays in regulating in the crossover/noncrossover
decision by enabling the creation of a specific class of crossovers that are distributed throughout
the genome. The third aim takes advantage of a major resource we developed in the last grant
period—namely a dataset containing thousands of phosphorylated amino acids on proteins
arrested in meiotic prophase. Phosphosites on proteins important for meiotic recombination and
synapsis will be mutated and phenotypically characterized to discover the functional role of the
phosphorylation. Two examples are provided for proteins we plan to pursue in the near future:
Ecm11—a SUMOylated protein that is necessary for SC formation and Red1, whose
degradation is mediated by Cdc5, resulting in SC disassembly and inactivation of Mek1 to allow
repair of residual DSBs prior to the onset of the first meiotic division.

## Key facts

- **NIH application ID:** 9983747
- **Project number:** 5R01GM050717-25
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Nancy M. Hollingsworth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $460,646
- **Award type:** 5
- **Project period:** 1995-01-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983747

## Citation

> US National Institutes of Health, RePORTER application 9983747, Analyis of meiotic chromosome synapsis in yeast (5R01GM050717-25). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9983747. Licensed CC0.

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