# Role of GCNA in preserving genome integrity and fertility

> **NIH NIH R01** · MAGEE-WOMEN'S RES INST AND FOUNDATION · 2022 · $452,706

## Abstract

PROJECT SUMMARY
We propose a cross-species approach to understand the pathways that maintain genome integrity in germ
cells. The perpetuation of the species requires that the genome is protected from endogenous and exogenous
threats. Nowhere is this more critical than in the germ cells, the precursors of egg and sperm. Defects in the
vigilance pathways lead to loss of genome integrity and subsequent deterioration of offspring vigor and/or
miscarriage. Detailed studies of a newly identified, highly conserved genetic factor, GCNA (Germ Cell Nuclear
Acidic Peptidase), will provide novel insights into key determinants of genome integrity and fertility. Our
preliminary data show that loss of GCNA results genomic instability in both Drosophila and C. elegans,
indicating conservation of function. The experiments outlined here will provide some of the first insights into the
shared mechanisms by which conserved GCNA family members promote genomic integrity and fertility across
species. We find that GCNA both interacts with Topoisomerase 2 and prevents the formation of DNA:protein
crosslinks (DPCs). GCNA mutant animals display increased chromosome loss, mutation accumulation, and
cell cycle defects, placing GCNA at the hub of multiple genome integrity processes. To explore the
mechanisms underlying gcna functions in germ cell maintenance, we propose three specific aims: 1) to
analyze the etiology of chromosome loss, and to determine the contribution of gcna to cell cycle regulation, 2)
to characterize the interaction with topoisomerase 2, identify conserved binding partners, and illuminate the
nature and etiology of DPCs, and 3) to understand the domain structure of GCNA and its functional relevance
to human fertility.

## Key facts

- **NIH application ID:** 10478296
- **Project number:** 5R01GM127569-04
- **Recipient organization:** MAGEE-WOMEN'S RES INST AND FOUNDATION
- **Principal Investigator:** Michael Buszczak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $452,706
- **Award type:** 5
- **Project period:** 2019-09-16 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478296

## Citation

> US National Institutes of Health, RePORTER application 10478296, Role of GCNA in preserving genome integrity and fertility (5R01GM127569-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10478296. Licensed CC0.

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