Partner Choice during Meiosis Is Regulated by Hop1-promoted Dimerization of Mek1

Abstract

Meiotic recombination differs from mitotic recombination in that DSBs are repaired using homologous chromosomes, rather than sister chromatids. This change in partner choice is due in part to a barrier to sister chromatid repair (BSCR) created by the meiosis-specific kinase, Mek1, in a complex with two other meiosis-specific proteins, Hop1 and Red1. HOP1 contains two functional domains, called the N and C domains. Analysis of a point mutation that specifically inactivates the C domain (hop1-K593A) reveals that the N domain is sufficient for Hop1 localization to chromosomes and for Red1 and Hop1 interactions. The C domain is needed for spore viability, for chromosome synapsis, and for preventing DMC1-independent DSB repair, indicating it plays a role in the BSCR. All of the hop1-K593A phenotypes can be bypassed by fusion of ectopic dimerization domains to Mek1, suggesting that the function of the C domain is to promote Mek1 dimerization. Hop1 is a DSB-dependent phosphoprotein, whose phosphorylation requires the presence of the C domain, but is independent of MEK1. These results suggest a model in which Hop1 phosphorylation in response to DSBs triggers dimerization of Mek1 via the Hop1 C domain, thereby enabling Mek1 to phosphorylate target proteins that prevent repair of DSBs by sister chromatids.

Red-Hed regulation: recombinase Rad51, though capable of playing the leading role, may be relegated to supporting Dmc1 in budding yeast meiosis: Figure 1.

“…Cold Spring Harbor Laboratory Press on March 22, 2019 -Published by genesdev.cshlp.org Downloaded from red1 and dmc1 mek1 (Schwacha and Kleckner 1997;Bishop et al 1999;Niu et al 2005) than in dmc1 hed1 (Tsubouchi and Roeder 2006). Further characterization of the interplay between the Red1 pathway and Hed1 should be illuminating.…”

“…Another important observation is that even when both recombinases are intact, mutation of the axial proteins can reduce the efficiency of interhomolog partner choice (Schwacha and Kleckner 1997;Wan et al 2004;Niu et al 2005). This indicates that cooperation of recombinases is not sufficient for normal partner choice.…”

“…Previous work showed that Dmc1-independent recombination is inhibited by proteins associated with axial elements (Schwacha and Kleckner 1997;Xu et al 1997;Bishop et al 1999;Niu et al 2005) proteinaceous structures that organize pairs of sister chromatids into two parallel sets of loops by binding at their base. The assembly of the synaptonemal complex brings an axial element with its pair of sisters into close parallel alignment with another axial element holding the homologous sister pair.…”

Linear Element-Independent Meiotic Recombination in Schizosaccharomyces pombe

“…This structural conservation and the absence of a visible SC in S. pombe strongly suggest that AEs serve some function other than providing a precursory platform for SC formation; they may function by contributing to the establishment of chromosomal mechanical forces of compaction, which have been proposed to regulate meiotic recombination (Blat et al 2002;Kleckner et al 2004). Furthermore, AEs (and possibly LinEs) appear to play a critical role in directing interhomolog recombination, precluding intersister recombination events (Schwacha and Kleckner 1997;Thompson and Stahl 1999), possibly by providing a platform for Hop1 protein-mediated dimerization of the Mek1 kinase, which, like Red1 and Hop1, is required to promote interhomolog recombination (Niu et al 2005).…”

Hed1 regulates Rad51-mediated recombination via a novel mechanism

“…In this regard, Red1, Hop1, and Mek1, which are associated with the cores of meiotic chromosomes, facilitate interhomolog crossover formation by attenuating the Rad51-only recombination pathway (Schwacha and Kleckner 1997;Xu et al 1997;Niu et al 2005).…”