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

Abstract

Meiotic recombination is highly regulated to ensure precise segregation of homologous chromosomes. Evidence from diverse organisms indicates that the synaptonemal complex (SC), which assembles between paired chromosomes, plays essential roles in crossover formation and patterning. Several additional "pro-crossover" proteins are also required for recombination intermediates to become crossovers. These typically form multiple foci or recombination nodules along SCs, and later accumulate at fewer, widely spaced sites. Here we report that in C. elegans CDK-2 is required to stabilize all crossover intermediates and stabilizes interactions among pro-crossover factors by phosphorylating MSH-5. Additionally, we show that the conserved RING domain proteins ZHP-3/4 diffuse along the SC and remain dynamic following their accumulation at recombination sites. Based on these and previous findings we propose a model in which recombination nodules arise through spatially restricted biomolecular condensation and then undergo a regulated coarsening process, resulting in crossover interference.

Dual control of meiotic crossover patterning

“…The results we present here and previous observations can be interpreted in the context of an emerging model for crossover patterning via droplet coarsening through the diffusion of HEI10 along the SC 5,6 . In this model (Figure 5), HEI10 initially forms multiple droplets along the SC, and HEI10 molecules diffuse along the SC from droplets to droplets.…”

Coarsening dynamics can explain meiotic crossover patterning in both the presence and absence of the synaptonemal complex

“…The SC likely acts as a conduit for HEI10 diffusion along synapsed pachytene bivalents (Morgan et al, 2021; Rog et al, 2017; Zhang et al, 2021, 2018). Without an SC, we postulated that HEI10 diffusion could instead occur through the nucleoplasm, with little or no movement along chromosomes, as has also previously been suggested from work in C. elegans (Zhang et al, 2021). We therefore investigated this hypothesis by developing a new coarsening model for crossover interference without an SC.…”

“…These aspects include: CO placement, CO frequency, CO assurance, cis-interference, trans-interference, CO homeostasis, heterochiasmy, meiotic duration, interchromosomal effects and diverse HEI10 focal intensity measurements. Given the conserved nature of HEI10 (Agarwal and Roeder, 2000; Chelysheva et al, 2012; Jantsch et al, 2004; Lake et al, 2015; Qiao et al, 2014; Reynolds et al, 2013), and the discovery of similar coarsening mechanisms in C. elegans (Zhang et al, 2021), it is likely that similar mechanisms regulate these same crossover patterning phenomena in a wide variety of sexually reproducing eukaryotes.…”

“…By the end of the pachytene substage of prophase I, HEI10 is retained at only a small number of predominantly distantly-spaced RIs, each with high levels of HEI10, which are then designated to become COs (Morgan et al, 2021). A similar model was subsequently proposed to underlie CO patterning in C. elegans (Zhang et al, 2021), suggesting that this molecular coarsening paradigm represents a conserved feature of meiotic CO control.…”

“…Instead, HEI10 is assumed to diffuse through a communal nucleoplasm, generating competition for HEI10 between RIs located on different bivalents. Similarly, in C. elegans , it has previously been suggested that the SC functions to prevent exchange of recombination proteins between RIs via the nucleoplasm (Rog et al, 2017; Zhang et al, 2021, 2018). Using our model, we provide a mechanistic explanation for why SC mutants lose both CO interference and assurance.…”