GCNA Preserves Genome Integrity and Fertility Across Species

Bhargava, V., Goldstein, C. D., Russell, L., Xu, L., Ahmed, M., Li, W., Casey, A., Servage, K., Kollipara, R., Picciarelli, Z., Kittler, R., Yatsenko, A., Carmell, M., Orth, K., Amatruda, J. F., Yanowitz, J. L., Buszczak, M. (December 2019) GCNA Preserves Genome Integrity and Fertility Across Species. Dev Cell, 52 (1). pp. 38-52. ISSN 1534-5807 (Public Dataset)

Abstract

The propagation of species depends on the ability of germ cells to protect their genome from numerous exogenous and endogenous threats. While these cells employ ubiquitous repair pathways, specialized mechanisms that ensure high-fidelity replication, chromosome segregation, and repair of germ cell genomes remain incompletely understood. We identified Germ Cell Nuclear Acidic Peptidase (GCNA) as a conserved regulator of genome stability in flies, worms, zebrafish, and human germ cell tumors. GCNA contains an acidic intrinsically disordered region (IDR) and a protease-like SprT domain. In addition to chromosomal instability and replication stress, Gcna mutants accumulate DNA-protein crosslinks (DPCs). GCNA acts in parallel with the SprT domain protein Spartan. Structural analysis reveals that while the SprT domain is needed to limit DNA damage, the IDR imparts significant function. This work shows that GCNA protects germ cells from various sources of damage, providing insights into conserved mechanisms that promote genome integrity across generations.

Item Type: Paper
Subjects: bioinformatics
organism description > animal > C elegans
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
diseases & disorders > neoplasms
organism description > animal
organism description > animal > bird
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA repair
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > germ cell
organism description > animal > insect
organism description > animal > bird > Zebra Finch
CSHL Authors:
Depositing User: Adrian Gomez
Date: 11 December 2019
Date Deposited: 19 Dec 2019 15:32
Last Modified: 01 Feb 2024 20:36
PMCID: PMC6946843
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/38782

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