Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans.

Aya Sato-Carlton,Chihiro Nakamura-Tabuchi,Xuan Li,Consuelo Barroso,Madison K Lehmer,Peter Mark Carlton,Scott C Rosenberg,Enrique Martinez-Perez,Kevin D Corbett,Hendrik Boog

doi:10.1371/journal.pgen.1008968

Abstract

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved "closure motif" region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.

Highlights

Meiosis reduces chromosome number from diploid to haploid by carrying out two rounds of chromosome segregation following a single round of DNA replication
To segregate properly in meiosis, cohesion between replicated chromosomes must remain after the first meiotic cell division, so chromosomes can be held together until they separate in the second division
We report here that the chromosome axis protein HIM-3 and its modification by phosphorylation is important for ensuring the robust establishment of short and long arm functions

Summary

Introduction

Meiosis reduces chromosome number from diploid to haploid by carrying out two rounds of chromosome segregation following a single round of DNA replication. Organisms whose chromosomes have single, defined centromeres (monocentric) lose cohesin from chromosome arms in meiosis I, while cohesin at centromeres is protected by the protein Shugoshin [reviewed in 1] until meiosis II. In C. elegans, each chromosome normally receives a single crossover (CO) [reviewed in 2], which divides the chromosome into two domains of unequal length termed the short and long arms [3,4]. At meiosis I, cohesion is removed from short arms, while cohesion on long arms persists until degraded at meiosis II, separating chromatids in two discrete steps [reviewed in 5]. Establishment of short and long arm domains must occur facultatively for each chromosome in each meiocyte

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