Cohesins: Chromosomal Proteins that Prevent Premature Separation of Sister Chromatids

Abstract

Cohesion between sister chromatids opposes the splitting force exerted by microtubules, and loss of this cohesion is responsible for the subsequent separation of sister chromatids during anaphase. We describe three chromosmal proteins that prevent premature separation of sister chromatids in yeast. Two, Smc1p and Smc3p, are members of the SMC family, which are putative ATPases with coiled-coil domains. A third protein, which we call Scc1p, binds to chromosomes during S phase, dissociates from them at the metaphase-to-anaphase transition, and is degraded by the anaphase promoting complex. Association of Scc1p with chromatin depends on Smc1p. Proteins homologous to Scc1p exist in a variety of eukaryotic organisms including humans. A common cohesion apparatus might be used by all eukaryotic cells during both mitosis and meiosis.

Characterization of the components of the putative mammalian sister chromatid cohesion complex

“…5B). This differs from the expression pattern displayed by Mcd1p in S. cerevisiae (Guacci et al, 1997;Michaelis et al, 1997), which is cell-cycle-dependent. Thus, regulation of PW29 in mouse fibroblasts differs from regulation of Mcd1p in S. cerevisiae.…”

“…The mode of their intracellular redistribution during mitosis was also analogous to the data obtained for overexpressed Mcd1p in budding yeast (Guacci et al, 1997). The relative abundance of the PW29 protein in mitosis was, however, in sharp contrast to mitosis in budding yeast where Mcd1p is significantly downregulated (Guacci et al, 1997;Michaelis et al, 1997).…”

“…In addition, the Mcd1 protein leaves chromosomes during anaphase in budding yeast, while Smc proteins remain associated with chromatin (Guacci et al, 1997;Michaelis et al, 1997). These observations suggest that in budding yeast, the composition of the cohesin complex varies throughout the cell cycle.…”

“…The S. cerevisiae proteins Smc1p, Smc3p and Mcd1p (also known as Scc1p) have well-established roles in sister chromatid cohesion (Michaelis et al, 1997;Strunnikov, 1998). The X. laevis homologs of these proteins, termed XSMC1, XSMC3 and XRAD21, along with two other proteins, are all components of a complex that promotes sister chromatid cohesion in vitro (Losada et al, 1998).…”

Functional links between Drosophila Nipped-B and cohesin in somatic and meiotic cells

“…Nipped-B encodes a member of a highly conserved protein family, which includes Scc2 and Mis4 of S. cerevisiae and S. pombe, discovered in screens for factors that control sister chromatid cohesion (Furuya et al 1998;Michaelis et al 1997), C. cinereus Rad9 identified in a screen for factors required for deoxyribonucleic acid (DNA) repair and meiosis (Valentine et al 1995), and human Nipped-B-Like (NIPBL/delangin), mutated in Cornelia de Lange syndrome (CdLS; Krantz et al 2004;Tonkin et al 2004). Nipped-B family proteins contain seven HEAT repeats implicated in protein-protein interactions (Neuwald and Hirano 2000), and NIPBL missense mutations in all seven cause CdLS Miyake et al 2005;Deardorff and Krantz, personal communication).…”