Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure

Abstract

Rec8 is a prominent component of the meiotic prophase chromosome axis that mediates sister chromatid cohesion, homologous recombination and chromosome synapsis. Here, we explore the prophase roles of Rec8. (i) During the meiotic divisions, Rec8 phosphorylation mediates its separase-mediated cleavage. We show here that such cleavage plays no detectable role for chromosomal events of prophase. (ii) We have analyzed in detail three rec8 phospho-mutants, with 6, 24 or 29 alanine substitutions. A distinct ‘separation of function’ phenotype is revealed. In the mutants, axis formation and recombination initiation are normal, as is non-crossover recombination; in contrast, crossover (CO)-related events are defective. Moreover, the severities of these defects increase coordinately with the number of substitution mutations, consistent with the possibility that global phosphorylation of Rec8 is important for these effects. (iii) We have analyzed the roles of three kinases that phosphorylate Rec8 during prophase. Timed inhibition of Dbf4-dependent Cdc7 kinase confers defects concordant with rec8 phospho-mutant phenotypes. Inhibition of Hrr25 or Cdc5/polo-like kinase does not. Our results suggest that Rec8's prophase function, independently of cohesin cleavage, contributes to CO-specific events in conjunction with the maintenance of homolog bias at the leptotene/zygotene transition of meiotic prophase.

Meiosis‐specific cohesin component, Rec8, promotes the localization of Mps3 SUN domain protein on the nuclear envelope

“…We also checked the effect of a hypomorph allele of rec8 , rec8–29A , which has substitutions of most of phosphorylated Ser/Thr residues on Rec8, and thus is defective in the phosphorylation (Brar et al, ; Katis et al, ), on Mps3 dynamics during meiosis. The rec8–29A mutant showed delay of prophase I events (Brar, Hochwagen, Ee, & Amon, ; Yoon et al, ), which is associated with a transient accumulation of Mps3 pattern (Figure e). Importantly, the rec8–29A transiently accumulated Mps3 cluster in early prophase I compared to wild type, for example, 4 hr, which is similar to that in the mutant in a cohesin regulator, Rad61/Wpl1 (Challa et al, ).…”

Atypical meiosis can be adaptive in outcrossedS. pombedue towtfmeiotic drivers

“…Sgo1 protects centromeric cohesion from cleavage and Moa1 promotes monopolar kinetochore attachment of sister chromosomes (Kitajima et al, 2004; Yokobayashi and Watanabe 2005). Finally, Rec8 is the meiotic kleisin that plays key roles in recombination and ensuring proper chromosome segregation in both meiotic divisions (Krawchuk et al, 1999; Watanabe and Nurse 1999; Yoon et al, 2016).…”

EWSR1 affects PRDM9-dependent histone 3 methylation and provides a link between recombination hotspots and the chromosome axis

“…In mice, loss of REC8 causes meiotic arrest, asynapsis and DSBs formation defects [57–59]. Moreover, in yeast and mammals, pREC8 is required for REC8 cleavage and meiotic prophase I progress [60–63], and is essential for crossover determination and SC formation [64]. Consequently, the EWSR1-dependent association between PRDM9-activated hotspots and pREC8 may promote proper DSB formation and crossover pathway choice, which can explain the altered DSB distribution, increased chromosomal asynapsis, and changes in crossover number and distribution that we observed in Ewsr1 CKO spermatocytes.…”