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

Four members of the structural maintenance of chromosome (SMC) protein family have essential functions in chromosome condensation (SMC2/4) and sister-chromatid cohesion (SMC1/3). The SMC5/6 complex has been implicated in chromosome replication, DNA repair, and chromosome segregation in somatic cells, but its possible functions during mammalian meiosis are unknown. Here, we find that in mouse spermatocytes SMC5 and SMC6 are located at the central region of the synaptonemal complex from zygotene until diplotene. During late diplotene both proteins load to the chromocenters, where they colocalize with DNA Topoisomerase IIα, and then accumulate at the inner domain of the centromeres during the first and second meiotic divisions. Interestingly, SMC6 and DNA Topoisomerase IIα colocalize at stretched strands that join kinetochores during the metaphase II to anaphase II transition, and are both observed on stretched lagging chromosomes at anaphase II following Etoposide treatment. During mitosis SMC6 and DNA Topoisomerase IIα colocalize at the centromeres and chromatid axes. Our results are consistent with the participation of SMC5 and SMC6 in homologous chromosome synapsis during prophase I, chromosome and centromere structure during meiosis I and mitosis, and, with DNA Topoisomerase IIα, in regulating centromere cohesion during meiosis II.