GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability

被引:41
作者
Dokshin, Gregoriy A. [1 ]
Davis, Gregory M. [2 ]
Sawle, Ashley D. [3 ]
Eldridge, Matthew D. [3 ]
Nicholls, Peter K. [4 ]
Gourley, Taylin E. [2 ]
Romer, Katherine A. [4 ,5 ]
Molesworth, Luke W. [2 ]
Tatnell, Hannah R. [2 ]
Ozturk, Ahmet R. [1 ]
de Rooij, Dirk G. [4 ,6 ,7 ,8 ]
Hannon, Gregory J. [3 ]
Page, David C. [4 ,9 ]
Mello, Craig C. [1 ,10 ]
Carmell, Michelle A. [1 ,4 ,8 ]
机构
[1] Univ Massachusetts, Sch Med, RNA Therapeut Inst, Worcester, MA 01605 USA
[2] Federat Univ, Sch Hlth & Life Sci, Clayton, Vic 3841, Australia
[3] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England
[4] Whitehead Inst, 455 Main St, Cambridge, MA 02142 USA
[5] MIT, Computat & Syst Biol Program, Cambridge, MA 02142 USA
[6] Univ Utrecht, Dept Biol, Fac Sci, Reprod Biol Grp,Div Dev Biol, NL-3584 Utrecht, Netherlands
[7] Univ Amsterdam, Acad Med Ctr, Ctr Reprod Med, NL-1105 Amsterdam, Netherlands
[8] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[9] Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
[10] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA
关键词
DOUBLE-STRAND BREAKS; CROSS-LINK REPAIR; DNA PHOSPHODIESTERASE; GENE-EXPRESSION; COPY NUMBER; STEM-CELLS; CHROMOSOMAL-ABERRATIONS; MEIOTIC RECOMBINATION; CHROMATIN STATES; SOMATIC-CELLS;
D O I
10.1016/j.devcel.2019.11.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:53 / +
页数:22
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