Recruitment of Polo-like kinase couples synapsis to meiotic progression via inactivation of CHK-2

Abstract

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.

Crossover patterning through kinase-regulated condensation and coarsening of recombination nodules

“…Evidence from Sordaria, mice, Drosophila, and many plants, in addition to C. elegans, has indicated that recombination nodules undergo a progression from many early foci to a more limited number of "crossover-designated" foci (Wettstein et al, 1984), which our model attributes to coarsening. In C. elegans this transition is regulated by CHK-2 activity so that it normally occurs only after complete assembly of the SC and establishment of JMs along all chromosomes (Zhang et al, 2021). However, we postulate that in other organisms, including budding yeast, coarsening may occur concomitant with SC assembly.…”

“…A related complex, ZHP-1/ZHP-2, is specifically required for the appearance of late foci, but these proteins remain distributed along the SC, rather than concentrating at foci. We recently reported that the transition from early to late foci in C. elegans is triggered by inactivation of CHK-2 kinase activity, which normally occurs at mid-pachytene (Zhang et al, 2021). Mutations that impair the formation of JMs along one or more chromosomes trigger a crossover assurance checkpoint, which delays the timing of CHK-2 inactivation and crossover designation (Yu et al, 2016).…”

A novel meiotic protein required for homolog pairing and regulation of synapsis in C. elegans

“…Nevertheless, CDK2, which inhibits inappropriate synapsis in mice is also recruited to LINC complexes (Mikolcevic et al, 2016; Viera et al, 2009; Tu et al, 2017; Chen et al, 2021), suggesting that regulation of synapsis may be a general role of chromosome-LINC complex attachments, despite some differences in the details of this regulation between organisms. Intriguingly, telomeric attachments in mammals and PC attachments in C. elegans each require a kinase (CDK2 and PLK-2, respectively) that is also involved in crossover regulation, suggesting that coordination between chromosome attachments sites and CO intermediates may be a conserved feature of meiosis (Woglar and Villeneuve, 2018; Zhang et al, 2021; Ashley and Rooij, 2001; Palmer et al, 2020).…”

“…(q782) qIs48] (I;III) . The following constructs were used for auxin-inducible degradation: zyg-12::ha::aid and aid::v5::sun-1 (Liu et al, 2021), ha::aid::chk-2 (Zhang et al, 2021) where “aid” designates a 44-amino acid degron sequence (Zhang et al, 2015).…”