GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability
Name
570200v1.full.pdf
Description
Submitted version
Size
2.79 MB
Format
Adobe PDF
Checksum (MD5)
438d066d0af0ef4af500ce23a70b57a4
Author(s)
Romer, Katherine A.
De Rooij, Dirk G.
Page, David C.
Carmell, Michelle A.
Date Issued
January 2020
Journal
Developmental cell
Publisher
Elsevier BV
Citation
Davis, Gregory M. et al. “GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability.” Developmental cell 52 (2020): 53-68.e6
Version
Original manuscript
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. DNA topoisomerases help unwind DNA but occasionally get trapped, resulting in DNA-protein crosslinks (DPCs). DPCs damage DNA and threaten genomic integrity. Dokshin et al. find that GCNA protein family complements standard DPC processing machinery in resolving topoisomerase II DPCs to ensure heritable genome stability and germline immortality.
MIT Department
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.devcel.2019.11.006
