Novel Meiosis-Specific Isoform of Mammalian SMC1

Abstract

Structural maintenance of chromosomes (SMC) proteins fulfill pivotal roles in chromosome dynamics. In yeast, the SMC1-SMC3 heterodimer is required for meiotic sister chromatid cohesion and DNA recombination. Little is known, however, about mammalian SMC proteins in meiotic cells. We have identified a novel SMC protein (SMC1β), which—except for a unique, basic, DNA binding C-terminal motif—is highly homologous to SMC1 (which may now be called SMC1α) and is not present in the yeast genome. SMC1β is specifically expressed in testes and coimmunoprecipitates with SMC3 from testis nuclear extracts, but not from a variety of somatic cells. This establishes for mammalian cells the concept of cell-type- and tissue-specific SMC protein isoforms. Analysis of testis sections and chromosome spreads of various stages of meiosis revealed localization of SMC1β along the axial elements of synaptonemal complexes in prophase I. Most SMC1β dissociates from the chromosome arms in late-pachytene-diplotene cells. However, SMC1β, but not SMC1α, remains chromatin associated at the centromeres up to metaphase II. Thus, SMC1β and not SMC1α is likely involved in maintaining cohesion between sister centromeres until anaphase II.

ACKNOWLEDGMENTS

We thank Mirjam van Aalderen for expert technical assistance and David Avila for protein sequencing. E.R. was supported by a grant from the Human Frontier of Science Foundation and by NIH grant GM62517. M.E. was financially supported by grant no. 901-01-097 of The Netherlands Society for Scientific Research (NWO).

An initial part of this work was done at the Basel Institute for Immunology, Basel, Switzerland.