4.7 Article

GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability

期刊

DEVELOPMENTAL CELL
卷 52, 期 1, 页码 53-+

出版社

CELL PRESS
DOI: 10.1016/j.devcel.2019.11.006

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资金

  1. NIH [P40 OD010440, R37 GM058800, P01 HD078253]
  2. Life Sciences Research Foundation
  3. American Cancer Society [129916-PF16-232-RMC]
  4. Cancer Research UK
  5. Royal Society Wolfson Research Professorship
  6. International C. elegans Gene Knockout Consortium

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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.

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