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Curr Biol. 2015 Jun 29;25(13):1694-706. doi: 10.1016/j.cub.2015.05.017. Epub 2015 Jun 4.

Esco1 Acetylates Cohesin via a Mechanism Different from That of Esco2.

Author information

1
Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
2
Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
3
Laboratory of Cancer Stem Cell Biology, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan.
4
Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake Koto-Ku, Tokyo 135-8550, Japan.
5
Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan. Electronic address: mbando@iam.u-tokyo.ac.jp.
6
Laboratory of Genome Structure and Function, Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; Graduate School of Agricultural and Life Sciences, University of Tokyo, 1-1-1 Yayoi Bunkyo-Ku, Tokyo 113-0032, Japan; CREST, JST, K's Gobancho, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan. Electronic address: kshirahi@iam.u-tokyo.ac.jp.

Abstract

Sister chromatid cohesion is mediated by cohesin and is essential for accurate chromosome segregation. The cohesin subunits SMC1, SMC3, and Rad21 form a tripartite ring within which sister chromatids are thought to be entrapped. This event requires the acetylation of SMC3 and the association of sororin with cohesin by the acetyltransferases Esco1 and Esco2 in humans, but the functional mechanisms of these acetyltransferases remain elusive. Here, we showed that Esco1 requires Pds5, a cohesin regulatory subunit bound to Rad21, to form cohesion via SMC3 acetylation and the stabilization of the chromatin association of sororin, whereas Esco2 function was not affected by Pds5 depletion. Consistent with the functional link between Esco1 and Pds5, Pds5 interacted exclusively with Esco1, and this interaction was dependent on a unique and conserved Esco1 domain. Crucially, this interaction was essential for SMC3 acetylation and sister chromatid cohesion. Esco1 localized to cohesin localization sites on chromosomes throughout interphase in a manner that required the Esco1-Pds5 interaction, and it could acetylate SMC3 before and after DNA replication. These results indicate that Esco1 acetylates SMC3 via a mechanism different from that of Esco2. We propose that, by interacting with a unique domain of Esco1, Pds5 recruits Esco1 to chromatin-bound cohesin complexes to form cohesion. Furthermore, Esco1 acetylates SMC3 independently of DNA replication.

PMID:
26051894
DOI:
10.1016/j.cub.2015.05.017
[Indexed for MEDLINE]
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