LAB-1 Targets PP1 and Restricts Aurora B Kinase upon Entrance into Meiosis to Promote Sister Chromatid Cohesion

Yonatan B Tzur,Yanjie Gu,Diana S Chu,Iain M Cheeseman,Saravanapriah Nadarajan,Carlos Egydio De Carvalho,Monica P Colaiácovo,Ivo Van Bostelen,R Scott Hawley

doi:10.1371/journal.pbio.1001378

Abstract

Author SummaryA critical step for achieving successful cell division is the regulation of how the cohesin complexes that bind sister chromatids are initially deposited, then maintained, and finally removed to allow the chromatids to separate into daughter cells. This is particularly challenging during meiosis, when the sister chromatids must remain partially connected to each other through the first division. In organisms that have a single focal centromere on each chromosome, such as mammals and flies, cohesin is protected through the first meiotic division by the protein Shugoshin, which binds the PP2A phosphatase. PP2A counteracts phosphorylation by the Aurora B kinase; if certain cohesins are phosphorylated by Aurora B they become targeted for removal, which allows the chromatids to separate. In the nematode C. elegans, the chromosomes lack a localized centromere and the predicted Shugoshin homolog is not required for protection of cohesins; instead, this function is executed in metaphase of the first meiotic division by the protein LAB-1. But it is not completely understood what leads to the deposition of cohesin prior to entry into meiosis and to its maintenance throughout early meiosis I. In this study, we show that LAB-1 is also required for the loading and maintenance of the cohesin complex. LAB-1 ensures that the chromatids are not separated prematurely, and thus enables the proper progression of events through prophase I of meiosis. We propose that LAB-1 may act at the onset of meiosis in a manner akin to Shugoshin, by recruiting the PP1 phosphatase to counteract Aurora B kinase, thereby ensuring sister chromatid cohesion.

Highlights

Establishment and subsequent removal of Sister Chromatid Cohesion (SCC) between sister chromatids is necessary to facilitate faithful segregation of chromosomes in mitosis and meiosis
We propose that LAB-1 targets the phosphatase 1 (PP1) homologs to the chromatin at the onset of meiosis I, thereby antagonizing AIR-2 and cooperating with the cohesin complex to promote sister chromatid association and normal progression of the meiotic program
To determine whether this defect results from a role for lab-1 in early meiosis, we examined the effects of lab-1 depletion on the various processes that take place earlier during prophase I (Figure S1)

Summary

Introduction

Establishment and subsequent removal of Sister Chromatid Cohesion (SCC) between sister chromatids is necessary to facilitate faithful segregation of chromosomes in mitosis and meiosis. The control of SCC establishment and removal is even more intricate, and many meiotic processes fail when SCC is compromised. In this specialized cell division program, one cycle of chromosome replication is followed by two consecutive rounds of chromosome segregation, reducing the chromosome number by half to produce haploid sperm and oocytes. When the SC disassembles, homologs remain attached to each other through chiasmata as a result of earlier crossover recombination events underpinned by flanking SCC. While studies from a number of organisms have revealed key insights into the regulation of SCC removal, far less is known about how the establishment of SCC is regulated

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