Cohesin removal precedes topoisomerase IIα-dependent decatenation at centromeres in male mammalian meiosis II

Abstract

Sister chromatid cohesion is regulated by cohesin complexes and topoisomerase IIα. Although relevant studies have shed some light on the relationship between these two mechanisms of cohesion during mammalian mitosis, their interplay during mammalian meiosis remains unknown. In the present study, we have studied the dynamics of topoisomerase IIα in relation to that of the cohesin subunits RAD21 and REC8, the shugoshin-like 2 (Schizosaccharomyces pombe) (SGOL2) and the polo-like kinase 1-interacting checkpoint helicase (PICH), during both male mouse meiotic divisions. Our results strikingly show that topoisomerase IIα appears at stretched strands connecting the sister kinetochores of segregating early anaphase II chromatids, once the cohesin complexes have been removed from the centromeres. Moreover, the number and length of these topoisomerase IIα-connecting strands increase between lagging chromatids at anaphase II after the chemical inhibition of the enzymatic activity of topoisomerase IIα by etoposide. Our results also show that the etoposide-induced inhibition of topoisomerase IIα is not able to rescue the loss of centromere cohesion promoted by the absence of the shugoshin SGOL2 during anaphase I. Taking into account our results, we propose a two-step model for the sequential release of centromeric cohesion during male mammalian meiosis II. We suggest that the cohesin removal is a prerequisite for the posterior topoisomerase IIα-mediated resolution of persisting catenations between segregating chromatids during anaphase II.

Rif1 Is Required for Resolution of Ultrafine DNA Bridges in Anaphase to Ensure Genomic Stability

“…Activity before Anaphase Before anaphase, cohesin is thought to shield centromeric DNA from topoisomerase II-mediated decatenation (Gó mez et al, 2013;Stanvitch and Moore, 2008;Toyoda and Yanagida, 2006). In line with this notion, premature removal of centromeric cohesin in (pro)metaphase after depletion of the cohesin protector Shugoshin1 (Sgo1), resulted in the visualization of PICHpositive UFBs in prometaphase cells ( Figures 2F-2H) (Wang et al, 2010).…”

Dynamic localization of SMC5/6 complex proteins during mammalian meiosis and mitosis implies functions in distinct chromosome processes

“…This is a potent Topo IIa inhibitor whose effect lies in blocking the activity of Topo IIa once it has cut the concatenated DNA molecules, but prior to the occurrence of the religation (Nitiss, 2009). Our previous data demonstrate that Etoposide induces the appearance of lagging chromosomes during the second meiotic division, and that the chromatids remain associated by Topo IIa strands joining their kinetochores (Gómez et al, 2013). Indeed, Etoposide does not disturb the chromosomal Topo IIa distribution, but only its enzymatic activity (Nitiss, 2009).…”

Topoisomerases modulate the timing of meiotic DNA breakage and chromosome morphogenesis inSaccharomyces cerevisiae

“…The meiotic functions of topoisomerases have been primarily elucidated in the context of the meiotic divisions where, similar to mitosis, topo II has a major role in disentangling DNA to facilitate chromosome segregation (Gomez et al, 2014;Hartsuiker et al, 1998;Hughes & Hawley, 2014;Jaramillo-Lambert et al, 2016;Kallio & Lahdetie, 1996;Mengoli et al, 2014;Tateno & Kamiguchi, 2001). However, both topoisomerases are also present and active in meiotic prophase (Borde et al, 1999;Cobb et al, 1997;Stern & Hotta, 1983).…”