RESEARCH HIGHLIGHTS GETTY CELL CYCLE Cycling through acetylation The cohesin complex, the core components separase. Borges et al. showed that Smc3 of which are structural maintenance of deacetylation also occurs in vitro in the presence chromosomes 1 (Smc1), Smc3 and sister chromatid of a nuclease that fragments chromosomal DNA cohesion 1 (Scc1), holds sister chromatids together but not cohesin. This suggests that the cohesin from their replication in S phase until their complex is protected from deacetylation when separation in mitosis, and the establishment of it is bound to chromosomes and that its cohesion depends on the acetylation of Smc3 by dissociation from chromosomes at anaphase the acetyltransferase establishment of cohesion 1 enables Smc3 deacetylation. (Eco1). Smc3 is deacetylated at anaphase, but But why is Smc3 deacetylation important? the importance of this, and the deacetylase To investigate this, both groups expressed a responsible, were unknown. Two groups now version of Eco1 that can be depleted from cells in identify Hos1 as the enzyme that deacetylates a t emperature‑sensitive manner. Beckouët et al. Smc3 in Saccharomyces cerevisiae, and reveal found that depletion of Eco1 causes cohesion an important role for the Smc3 acetylation– defects and that these cells inherit little or no deacetylation cycle in establishing sister acetylated Smc3 from the previous cell cycle in chromatid cohesion. the presence of Hos1, as expected. Although To identify the Smc3 deacetylase, Borges et al. acetylated Smc3 persists in the next cell cycle in and Beckouët et al. screened 11 S. cerevisiae the absence of Eco1 and Hos1, this does not strains, each of which had one of the 11 known rescue cohesion defects. Borges et al. also show deacetylase genes deleted, for acetylated Smc3. that depletion of Hos1, which results in increased Increased levels of acetylated Smc3 were levels of acetylated Smc3, does not compensate observed in extracts from Hos1‑null cells under for reduced Eco1 function. These data suggest various conditions, including in G1‑arrested cells that it is the de novo acetylation of unacetylated (which do not normally have acetylated Smc3), Smc3 that is essential for establishing cohesion indicating that Hos1 is the Smc3 deacetylase. during S phase. So, why is Smc3 deacetylation triggered at In short, these papers show that Hos1 anaphase? At the onset of anaphase Scc1 is deacetylates Smc3 at anaphase, after cohesin cleaved by separase, which releases cohesin has been released from the chromosomes, to from chromosomes to trigger chromosome ensure that there is a pool of unacetylated Smc3 segregation. Expression of a Scc1 variant that available for de novo Eco1‑mediated acetylation, cannot be cleaved by separase prevents Smc3 and thus efficient cohesion, in the next cell cycle. deacetylation, whereas cells expressing a Scc1 Katharine H. Wrighton variant that is cleaved when the tobacco etch virus protease is expressed undergo Smc3 ORIGINAL RESEARCH PAPERS Borges, V. et al. Hos1 deacetylation. These data suggest that Scc1 deacetylates Smc3 to close the cohesin acetylation cycle. Mol. Cell 39, 677–688 (2010) | Beckouët, F. et al. An Smc3 acetylation cycle is cleavage is necessary to trigger deacetylation. essential for establishment of sister chromatid cohesion. Mol. Cell To confirm this in vitro Beckouët et al. 39, 689–699 (2010) reconstituted Smc3 deacetylation and found that FURTHER READING Hirano, T. At the heart of the chromosome: SMC proteins in action. Nature Rev. Mol. Cell Biol. 7, 311–322 (2006) it is effective in the presence of Hos1 and active NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 11 | NOVEMBER 2010 © 2010 Macmillan Publishers Limited. All rights reserved.