# Investigating the Role of CDK-2 in Meiotic Recombination

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2022 · $21,494

## Abstract

Sexually reproducing organisms rely on proper chromosome segregation during meiosis to ensure the
production of gametes with the complete genetic complement. During meiotic prophase I, chromosomes pair
and undergo chromosomal crossover, an exchange of genetic information between two homologous
chromosomes. This process leads to the formation of physical linkages between the homologs and enables each
chromosome pair to separate during meiosis I. Defects in crossover formation can be disastrous, leading to
aneuploidy and conditions such as age-related infertility, miscarriages, and Down Syndrome. Despite the
importance of this process, the mechanisms governing crossover formation remain poorly understood. The goal
of this project is to determine how crossovers are designated during meiosis to achieve faithful transmission of
genetic information. A recent genetic screen in C. elegans has identified a cyclin-like protein COSA-1 that is
essential for processing meiotic DNA double-strand breaks into crossovers. This finding was subsequently
followed by the identification of its mammalian ortholog CNTD1, which has conserved roles in crossover
formation. However, no CDK has been identified as a binding partner of COSA-1/CNTD1, and how these cyclin-
like proteins designate crossovers is not known. Recently, I have discovered that the C. elegans homolog of
CDK2 (CDK-2) localizes to the sites of crossovers, raising the possibility that CDK2 might partner with COSA-
1/CNTD1 and function as an active kinase to promote crossover formation. Supporting this idea, mammalian
CDK2 has long been observed at crossovers as well as telomeres. However, due to its telomeric function, CDK2
knockout mice exhibit severe defects in homolog pairing and synapsis, which are prerequisite to meiotic
recombination. Therefore, the role of CDK-2 at crossover sites has remained untested. Here I propose to use C.
elegans as a model system to investigate the conserved function of CDK2 in meiotic recombination. Unlike the
mammalian CDK2, CDK-2 is dispensable for homolog pairing and synapsis, but is specifically required for
crossover formation. In Aim 1 I will employ the auxin-inducible degradation system to determine the effect of
CDK-2 depletion on recombination machineries by super-resolution microscopy. I will also determine whether
CDK-2 and COSA-1 form an active kinase complex using purified components. In Aim 2 I will establish the
mechanisms by which CDK2 designates crossovers by identifying its meiotic substrates through both candidate-
based and unbiased chemical genetic approaches. I will then determine the functional significance of CDK2
targets through targeted mutagenesis in C. elegans. Overall, the results of this work will elucidate the conserved
regulatory mechanisms that designate crossovers and will be broadly applicable to higher eukaryotes. Johns
Hopkins University offers a state of-the-art research environment, strong records of post-graduate success, a
vast region...

## Key facts

- **NIH application ID:** 10470792
- **Project number:** 5F31HD100142-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jocelyn Haversat
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $21,494
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-10-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470792

## Citation

> US National Institutes of Health, RePORTER application 10470792, Investigating the Role of CDK-2 in Meiotic Recombination (5F31HD100142-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10470792. Licensed CC0.

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