| Structural highlights
Function
[ESCO1_HUMAN] Acetyltransferase required for the establishment of sister chromatid cohesion and couple the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during S phase. Acts by mediating the acetylation of cohesin component SMC3.[1] [2] [3] [4]
Publication Abstract from PubMed
Sister chromatid cohesion, formed by the cohesin protein complex, is essential for chromosome segregation. In order for cohesion to be established, the cohesin subunit SMC3 needs to be acetylated by a homolog of the ESCO1/Eco1 acetyltransferases, the enzymatic mechanism of which has remained unknown. Here we report the crystal structure of the ESCO1 acetyltransferase domain in complex with acetyl-coenzyme A, and show by SAXS that ESCO1 is a dimer in solution. The structure reveals an active site that lacks a potential catalytic base side chain. However, mutation of glutamate 789, a surface residue that is close to the automodification target lysine 803, strongly reduces autoacetylation of ESCO1. Moreover, budding yeast Smc3 mutated at the conserved residue D114, adjacent to the cohesion-activating acetylation site K112,K113, cannot be acetylated in vivo. This indicates that ESCO1 controls cohesion through substrate-assisted catalysis. Thus, this study discloses a key mechanism for cohesion establishment.
Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis.,Kouznetsova E, Kanno T, Karlberg T, Thorsell AG, Wisniewska M, Kursula P, Sjogren C, Schuler H Structure. 2016 May 3;24(5):789-96. doi: 10.1016/j.str.2016.03.021. Epub 2016 Apr, 21. PMID:27112597[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bellows AM, Kenna MA, Cassimeris L, Skibbens RV. Human EFO1p exhibits acetyltransferase activity and is a unique combination of linker histone and Ctf7p/Eco1p chromatid cohesion establishment domains. Nucleic Acids Res. 2003 Nov 1;31(21):6334-43. PMID:14576321
- ↑ Hou F, Zou H. Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion. Mol Biol Cell. 2005 Aug;16(8):3908-18. Epub 2005 Jun 15. PMID:15958495 doi:http://dx.doi.org/E04-12-1063
- ↑ Zhang J, Shi X, Li Y, Kim BJ, Jia J, Huang Z, Yang T, Fu X, Jung SY, Wang Y, Zhang P, Kim ST, Pan X, Qin J. Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast. Mol Cell. 2008 Jul 11;31(1):143-51. doi: 10.1016/j.molcel.2008.06.006. PMID:18614053 doi:http://dx.doi.org/10.1016/j.molcel.2008.06.006
- ↑ Terret ME, Sherwood R, Rahman S, Qin J, Jallepalli PV. Cohesin acetylation speeds the replication fork. Nature. 2009 Nov 12;462(7270):231-4. PMID:19907496 doi:nature08550
- ↑ Kouznetsova E, Kanno T, Karlberg T, Thorsell AG, Wisniewska M, Kursula P, Sjogren C, Schuler H. Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis. Structure. 2016 May 3;24(5):789-96. doi: 10.1016/j.str.2016.03.021. Epub 2016 Apr, 21. PMID:27112597 doi:http://dx.doi.org/10.1016/j.str.2016.03.021
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