# Meiotic recombination in budding yeast

> **NIH NIH R35** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $294,723

## Abstract

Fundamental to sexual reproduction is the ability to make gametes, such as sperm and eggs in
humans, which contain only one copy of each chromosome. Fertilization then results in the fusion of two
haploid gametes to create a diploid organism. For organisms such as budding yeast and humans, this is a
daunting task, as there are 16 and 23 pairs of chromosomes, respectively, that must be properly sorted into
each gamete. Meiosis is the specialized cell division that divides the chromosome number in half by having
one round of DNA replication followed by two rounds of chromosome segregation. Failure to properly
segregate chromosomes during meiosis produces chromosomally imbalanced gametes, resulting in infertility
and birth defects such as Trisomy 21 (Down Syndrome).
 A critical part of meiosis is the first meiotic division, where homologous chromosomes are segregated
to opposite poles of the spindle. Crossovers are created by the reciprocal exchange of DNA between
homologs. Crossovers, in combination with sister chromatid cohesion, physically connect homologs so they
can align and properly segregate at the first meiotic division. Crossovers result from the repair of double strand
breaks that are deliberately introduced into chromosomes to initiate recombination. Because unrepaired double
strand breaks are lethal, meiotic recombination is a highly regulated process that ensures that every pair of
homologs receives at least one crossover and that all double strand breaks are repaired before the first meiotic
division.
 Studying meiosis directly in mammals is difficult as it is hard to access germ cells and the cells are
diploid, making it challenging to find recessive mutations. The budding yeast, Saccharomyces cerevisiae, has
been an excellent model system for studying meiosis because of the sophisticated genetic, biochemical,
molecular and cell biological tools that are available. The focus of my research has been on identifying genes
required for meiotic recombination and defining the molecular mechanisms by which these genes function
and/or are regulated. In particular, my lab has developed novel approaches for studying how phosphorylation
regulates recombination during meiosis, with an emphasis on the meiosis-specific kinase, Mek1 and the
conserved cell cycle kinase, Cdc7-Dbf4.
 Although immense progress has been made in our understanding of meiotic recombination, there are
still critical gaps that need to be filled. For example, there are many genes that contribute to the fidelity of
meiotic double strand break repair which remain to be discovered. Over the next five years, my lab plans to
study two genes we have identified that were previously unknown to play a role in meiosis: SEN1 and RRM3.
Sen1 is a helicase that unwinds RNA/DNA hybrids called R-loops in mitotically dividing cells and is essential
for life. Its mammalian ortholog, Senataxin, is required for meiosis. Rrm3 is a member of the conserved Pif1
DNA helicase family that is well know...

## Key facts

- **NIH application ID:** 10155941
- **Project number:** 1R35GM140684-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Nancy M. Hollingsworth
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $294,723
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155941

## Citation

> US National Institutes of Health, RePORTER application 10155941, Meiotic recombination in budding yeast (1R35GM140684-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155941. Licensed CC0.

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