# Role of Chromosomally Tethered Proteasome in Chromosome Pairing and Meiotic Recombination

> **NIH NIH R01** · CLEVELAND STATE UNIVERSITY · 2021 · $487,809

## Abstract

Project Summary
Meiotic chromosome segregation is essential for gamete formation in all sexually reproducing organisms,
including humans. Prior to segregation, homologous chromosomes (homologs) undergo pairing and
recombination giving rise to crossovers. Crossovers provide physical connections that mediate bipolar
homolog segregation. Without crossovers, gametes with unbalanced chromosome content form, a condition
associated with birth defects and sterility. Crossovers are formed by induction of double strand breaks (DSBs)
at multiple chromosome positions. The principal investigator’s long term goal is to understand the functional
integration of meiotic chromosome structure, and recombination. The current proposal aims to identify the role
of the 26S proteasome along meiotic chromosomes. We have recently discovered that the 26S proteasome is
recruited in an evolutionarily conserved manner to meiotic chromosomes where it is required for pairing of
homologous chromosomes and recombination. The proteasome is the main site of protein degradation in all
eukaryotes. It is a multicomponent, compartmentalized protease that resides both in the cytoplasm and the
nucleus. While cytoplasmic proteasome functions in eliminating misfolded and short-lived, regulatory proteins
have been recognized for a long time, functions of the proteasome in the nucleus are much less understood.
Using a combination of microscopy, genetic and proteomic approaches, we will pursue the following aims:
First, we will use tightly controlled conditional alleles to systematically characterize the contribution of the
proteasome to distinct meiotic functions. Second, we will identify degradation substrates of the proteasome
relevant for chromosome pairing and recombination, thereby providing insights into a novel class of molecules
that coordinate the meiotic program by preventing precocious progression of a subset of chromosomal events.
Meiotic chromosome segregation defects in absence of a functional proteasome emphasize the importance of
an improved understanding of this process. We will determine the overall composition of the proteasome and
factors that control its localization to distinct positions along meiotic chromosomes. These studies provide a
unique opportunity to determine to what extent proteolytic core and potentially alternative regulatory
proteasome particles cooperate along meiotic chromosomes. This analysis of proteasome functions in
recombination and homolog pairing will pave the way towards a better understanding how chromosome-
associated proteolysis is used in living cells, and how interference with proteasome function, e.g. in cancer
therapy, can impact fertility and reproductive health.

## Key facts

- **NIH application ID:** 10071877
- **Project number:** 5R01GM125800-04
- **Recipient organization:** CLEVELAND STATE UNIVERSITY
- **Principal Investigator:** Valentin Boerner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $487,809
- **Award type:** 5
- **Project period:** 2018-01-22 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071877

## Citation

> US National Institutes of Health, RePORTER application 10071877, Role of Chromosomally Tethered Proteasome in Chromosome Pairing and Meiotic Recombination (5R01GM125800-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10071877. Licensed CC0.

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