Meeting on Meiotic Divisions and Checkpoints

Introduction Meiosis is a special type of cell division through which haploid gametes are generated from diploid parent cells. This is accomplished by a first division that induces homologous chromosome segregation followed by a second mitosis-like division that promotes sister chromatid separation. During the prophase of meiosis I, three basic events take place: pairing of homologous chromosomes, synapsis and recombination. Pairing or alignment of homologous chromosomes allows chromosome stabilization by the formation of the synaptonemal complex, whereas synapsis facilitates the subsequent recombination events. The synaptonemal complex is a proteinaceous structure formed by lateral elements and transverse filaments (Fig 1; Page & Hawley, 2004). The lateral elements comprises cohesins (Rec8/C(2)M/SYN1, STAG3/Rec11, SMC1-b and SMC3), the structural proteins SCP2 and SCP3, and the HORMA-domain proteins Hop1/HIM3/Asy1 and Red1; the transverse filaments are formed by the proteins Zip1, SCP1, C(3)G and SYP1. Once the synaptonemal complex is assembled, crossover recombination events take place between homologous partners. Crossovers form temporary connections or chiasmata that hold homologues together and allow their correct attachment to the meiosis I spindle. However, in most vertebrate oocytes, spindle I formation and germinal vesicle breakdown (GVBD) is preceded by an arrest at prophase I. This arrest is maintained until progesterone stimulates re-entry into the meiotic cycle by inducing the polyadenylation and translation of several dormant mRNAs that encode proteins such as Mos or cyclin B. Translation of Mos and cyclin B activates the maturation-promoting factor (MPF) and thereby induces spindle formation and GVBD. Homologous chromosomes then attach to the spindle and when aligned correctly along the metaphase plate, they segregate—a process that in some species is regulated, at least in part, by the ubiquitin-dependent degradation of different substrates by the anaphase-promoting complex (APC; Tunquist & Maller, 2003). Subsequently, oocytes go through meiosis II and arrest at metaphase II owing to the cytostatic factor (CSF) until fertilization, which finally induces exit from metaphase II and cytokinesis. The correct completion of all these meiotic events is assured by various checkpoints, such as the DNAdamage checkpoint at pachytene stage and the spindle checkpoint at metaphase–anaphase transitions. In the opening lecture of this meeting, T. Hunt (Herts, UK) began by honouring Andre Picard, one of the pioneers of the study of meiotic division in starfish, who died in November 2004. Hunt then introduced some of the key mechanisms that regulate meiotic and mitotic cell cycles, such as the control of MPF activity by celldivision-cycle protein 25 (Cdc25), Wee1, CDK-activating kinase (CAK) and the APC, the activity of CSF, the role of the different cyclins and the regulation of cyclin B/Cdc2 and cyclin A/Cdc2 by the spindle checkpoint. Finally, he highlighted some unanswered questions, including the identity of the calmodulin kinase II substrate on metaphase II exit, the elucidation of the mechanisms that regulate APC activity, the identification of the phospho-protein pattern that is present during meiosis and mitosis, and the role of the