GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability

Dokshin, G. A., Davis, G. M., Sawle, A. D., Eldridge, M. D., Nicholls, P. K., Gourley, T. E., Romer, K. A., Molesworth, L. W., Tatnell, H. R., Ozturk, A. R., de Rooij, D. G., Hannon, G. J., Page, D. C., Mello, C. C., Carmell, M. A. (December 2019) GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability. Dev Cell. ISSN 1534-5807 (Public Dataset)

Abstract

GCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan (DVC-1) and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. Here, we show that GCNA mutants in mouse and C. elegans display defects in genome maintenance including DNA damage, aberrant chromosome condensation, and crossover defects in mouse spermatocytes and spontaneous genomic rearrangements in C. elegans. We show that GCNA and topoisomerase II (TOP2) physically interact in both mice and worms and colocalize on condensed chromosomes during mitosis in C. elegans embryos. Moreover, C. elegans gcna-1 mutants are hypersensitive to TOP2 poison. Together, our findings support a model in which GCNA provides genome maintenance functions in the germline and may do so, in part, by promoting the resolution of TOP2 DPCs.

Item Type:	Paper
Uncontrolled Keywords:
Subjects:	bioinformatics organism description > animal > C elegans bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA repair bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes organism description > animal > mammal organs, tissues, organelles, cell types and functions > organelles, types and functions > mitosis organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations organs, tissues, organelles, cell types and functions > organelles, types and functions organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > pluripotency bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > topoisomerase
CSHL Authors:	Hannon, Gregory J. Carmell, Michelle A.
Communities:	CSHL labs > Hannon lab
Depositing User:	Adrian Gomez
Date:	4 December 2019
Date Deposited:	19 Dec 2019 15:26
Last Modified:	02 Feb 2024 14:47
PMCID:	PMC7227305
Related URLs:	Publisher
Dataset ID:	SRA: SRP186577 GenBank Bioproject: PRJNA523775 GenBank Bioproject: PRJNA593070
URI:	https://repository.cshl.edu/id/eprint/38781

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