| Literature DB >> 31839538 |
Gregoriy A Dokshin1, Gregory M Davis2, Ashley D Sawle3, Matthew D Eldridge3, Peter K Nicholls4, Taylin E Gourley2, Katherine A Romer5, Luke W Molesworth2, Hannah R Tatnell2, Ahmet R Ozturk1, Dirk G de Rooij6, Gregory J Hannon7, David C Page8, Craig C Mello9, Michelle A Carmell10.
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.Entities:
Keywords: DNA-protein crosslink (DPC) repair; DVC-1; GCNA; Spartan; SprT; Top1; Top2; germ cells; topoisomerase
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Year: 2019 PMID： 31839538 PMCID： PMC7227305 DOI： 10.1016/j.devcel.2019.11.006
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270