# Elucidating a new function for Topoisomerase II in meiotic chromosome segregation

> **NIH NIH R03** · UNIVERSITY OF DELAWARE · 2020 · $76,216

## Abstract

PROJECT SUMMARY/ABSTRACT
The instructions that guide the normal operations of a cell are contained within its DNA. In each cell the
DNA is packaged into structures called chromosomes. Cells constantly divide to produce new cells that
replace cells that are worn-out. During the process of division, it is of utmost importance that the
chromosomes remain intact and that the correct number of chromosomes is distributed to each new cell.
Changes in chromosome structure and number within cells can disrupt basic cellular functions leading to
cancer. It is also essential that the reproductive cells, eggs and sperm, have the correct number of
chromosomes and that these chromosomes also have the correct structure. In the event that the
chromosome structure or number is compromised (aneuploidy) in eggs or sperm, the resulting offspring
may fail to develop properly. Cancer treatments often have negative side effects including secondary
tumors and infertility. The DNA disentangling enzyme Topoisomerase II (Topo II) is an important target of
several anti-cancer drugs. The normal function of this enzyme is to unknot and untangle DNA as cells go
through mitosis. Topoisomerase II is present in many different cells including cells that are undergoing the
specialized cell division of meiosis. The roles of Topo II have been extensively studied in mitosis, but
much less is known about its normal function in the meiotic cell cycle. Our long-term goal is to understand
the molecules and systems that ensure that each cell receives the correct number of chromosomes during
meiosis. In this proposal, we will investigate how Topo II interacts with the known players involved in
maintaining chromosome structure during meiosis (Aim 1) and we will identify the components that make
sure that Topoisomerase II operates at the correct time and place during this cell division (Aim 2).
Additionally, both of these aims will address how Topo II differentially contributes to meiosis in male and
female germ lines. Utilizing a temperature-sensitive allele of topo II [C. elegans top-2(it7ts)] as a unique
tool the proposed research will address the following goals: In Specific Aim 1, a combination of live cell
imaging and cytological approaches will be used to characterize the role of top-2 in male and female
meiosis and the relationship between TOP-2, the meiotic cohesins, and Aurora B kinase. Specific Aim 2
will elucidate the mechanisms of TOP-2 regulation during male and female meiosis using a proteomics
approach. Ultimately, this research will contribute to our understanding of how chromosomes are properly
segregated to prevent the formation of aneuploid gametes that lead to birth defects. In the future, we hope
this research may lead to the identification of potential therapeutic targets to prevent the formation of
aneuploid gametes.

## Key facts

- **NIH application ID:** 9881328
- **Project number:** 5R03HD098244-02
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Aimee Jaramillo-Lambert
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,216
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881328

## Citation

> US National Institutes of Health, RePORTER application 9881328, Elucidating a new function for Topoisomerase II in meiotic chromosome segregation (5R03HD098244-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9881328. Licensed CC0.

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