title: 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.
authors.affiliation: Unidad de Biología Celular, Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Gómez
authors.forename: Alberto
authors.initials: A
authors.lastname: Viera
authors.forename: Inés
authors.initials: I
authors.lastname: Berenguer
authors.forename: Elena
authors.initials: E
authors.lastname: Llano
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pendás
authors.forename: José Luis
authors.initials: JL
authors.lastname: Barbero
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kikuchi
authors.forename: José A
authors.initials: JA
authors.lastname: Suja
mesh_terms: D000705:Anaphase / Q000187:drug effects; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002503:Centromere / Q000187:drug effects / Q000378:metabolism*; D002842:Chromatids / Q000187:drug effects / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D008297:Male; D008322:Mammals / Q000378:metabolism*; D008540:Meiosis / Q000187:drug effects; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects; D000097722:Cohesins
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D005047:Etoposide; D000097722:Cohesins