RT Journal Article
SR Electronic
T1 Meiotic cell cycle progression requires adaptation to a constitutive DNA damage signal
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.20.449183
DO 10.1101/2021.06.20.449183
A1 Liangyu Zhang
A1 Weston T. Stauffer
A1 Andrew Ziesel
A1 John S. Wang
A1 Zhouliang Yu
A1 Nancy M. Hollingsworth
A1 Abby F. Dernburg
YR 2021
UL http://biorxiv.org/content/early/2021/06/21/2021.06.20.449183.abstract
AB Meiotic chromosome segregation relies on synapsis and crossover recombination between homologous chromosomes. These processes require multiple steps that are coordinated by the meiotic cell cycle and monitored by surveillance mechanisms. In the nematode Caenorhabditis elegans, CHK-2 kinase is activated at meiotic entry; its activity is essential for homologous synapsis and DSB formation. CHK-2 is normally inactivated at mid-prophase, but how this occurs has not been established. Defects in synapsis or establishment of crossover intermediates delay meiotic progression by prolonging the activity of CHK-2. We report that CHK-2 is necessary and sufficient to inhibit crossover designation. We further find that CHK-2 is inactivated at mid-prophase by a pathway that mediates DNA damage checkpoint adaptation in proliferating human cells: Polo-like kinases, particularly PLK-2, phosphorylate and inhibit CHK-2 in response to formation of crossover intermediates. These findings help to illuminate the mechanisms of crossover assurance and meiotic cell cycle control.Competing Interest StatementThe authors have declared no competing interest.