Summary
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 show in mouse spermatocytes that 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 both are observed on stretched lagging chromosomes at anaphase II following treatment with Etoposide. 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.
Author contributions
R.G., P.W.J., M.A.H. and J.A.S. conceived and designed the experiments. R.G., P.W.J., M.A.H. and J.A.S. performed the experiments. R.G., P.W.J., A.V., M.A., T.F., R.J., E.L., A.M.P., M.A.H. and J.A.S. analysed data. R.G., P.W.J., M.A.H. and J.A.S. wrote the manuscript.
Funding
This work was supported by Ministerio de Economía y Competitividad (Spain) [grant number SAF2011-28842-C02-01 to J.A.S. and SAF2011-25252 to A.M.P.]; a UK-US Fulbright Distinguished Scholar Award; the US National Institutes of Health [grant number HD069458 to P.W.J.; HD33816 to M.A.H.; HD42137 to John Eppig, M.A.H. and J.C.S.]; the Priority Program SPP 1384 ‘Mechanisms of genome haploidization’ (to M.A. and R.J.) from the German Science Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the NIH. Deposited in PMC for release after 12 months.
