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GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability
- Source :
- Other repository, Developmental cell, 52(1), 53-68.e6. Cell Press, Developmental Cell, 52(1), 53. Cell Press
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
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.<br />National Institutes of Health (U.S.) (Grant P40 OD010440)
- Subjects :
- germ cells
DNA damage
Mutant
Biology
General Biochemistry, Genetics and Molecular Biology
Germline
03 medical and health sciences
SprT
0302 clinical medicine
Homologous chromosome
Germ cells
Top1
Molecular Biology
Mitosis
030304 developmental biology
Top2
topoisomerase
0303 health sciences
Topoisomerase
DNA replication
Spartan
Embryo
Cell Biology
GCNA
Cell biology
DNA-protein crosslink (DPC) repair
biology.protein
DVC-1
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 15345807
- Database :
- OpenAIRE
- Journal :
- Other repository, Developmental cell, 52(1), 53-68.e6. Cell Press, Developmental Cell, 52(1), 53. Cell Press
- Accession number :
- edsair.doi.dedup.....9161fdf69b9eeb35d3bdc53e672a8e14