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:	organism description > animal > C elegans organism description > animal > insect > Drosophila 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
CSHL Authors:	Carmell, Michelle A.
Depositing User:	Adrian Gomez
Date:	11 December 2019
Date Deposited:	19 Dec 2019 15:32
Last Modified:	29 Jun 2021 18:51
PMCID:	PMC6946843
Related URLs:	Publisher
Dataset ID:	GEO: GSE127220
URI:	https://repository.cshl.edu/id/eprint/38782

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