Acetylation of SMC3 subunit of centromeric chromatin associated cohesin by ESCO1 or ESCO2

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R-HSA-2473152
Type
Reaction [transition]
Species
Homo sapiens
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Acetyltransferases ESCO1 and ESCO2 are homologs of the S. cerevisiae acetyltransferase Eco1, essential for viability in yeast. ESCO1 and ESCO2 share sequence homology in the C-terminal region, consisting of a H2C2 zinc finger motif and an acetyltransferase domain (Hou and Zou 2005). Both ESCO1 and ESCO2 acetylate the cohesin subunit SMC3 on two lysine residues, K105 and K106 (Zhang et al. 2008), an important step in the establishment of sister-chromatid cohesion during the S-phase of the cell cycle. Divergent N-termini of ESCO1 and ESCO2, necessary for chromatin binding, suggest that ESCO1 and ESCO2 may perform distinct functions in sister chromatid cohesion (Hou and Zou 2005). Several studies suggest that ESCO2 may be predominantly involved in acetylation of the SMC3 subunit of centromeric cohesin. A conditional targeting of Esco2 locus in mice leads to pre-implantational loss of homozygous Esco2 -/- embryos at the eight-cell stage. Prometaphase chromosomes isolated from two-cell stage Esco2 knockout embryos show marked cohesion defect at centromeres (Whelan et al. 2012). ESCO2 protein appears in the S-phase (Hou and Zou 2005, Whelan et al. 2012) and in mouse embryonic fibroblasts Esco2 predominantly localizes to pericentric heterochromatin (Whelan et al. 2012). Mutations in the ESCO2 gene (Vega et al. 2005) that impair ESCO2 acetyltransferase activity (Gordillo et al. 2008) are the cause of the Roberts syndrome, an autosomal recessive disorder characterized by craniofacial and limb abnormalities, and intellectual disability. Metaphase chromosomes of Roberts syndrome patients exhibit loss of cohesion at heterochromatic regions of centromeres and the Y chromosome, with a characteristic 'railroad track appearance' (Van den Berg and Francke 1993, Vega et al. 2005).

Literature References
PubMed ID Title Journal Year
8291532 Roberts syndrome: a review of 100 cases and a new rating system for severity

Van Den Berg, DJ, Francke, U

Am. J. Med. Genet. 1993
15958495 Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion

Hou, F, Zou, H

Mol. Biol. Cell 2005
15821733 Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion

Vega, H, Waisfisz, Q, Gordillo, M, Sakai, N, Yanagihara, I, Yamada, M, van Gosliga, D, Kayserili, H, Xu, C, Ozono, K, Jabs, EW, Inui, K, Joenje, H

Nat. Genet. 2005
22101327 Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatin

Whelan, G, Kreidl, E, Wutz, G, Egner, A, Peters, JM, Eichele, G

EMBO J. 2012
18411254 The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity

Gordillo, M, Vega, H, Trainer, AH, Hou, F, Sakai, N, Luque, R, Kayserili, H, Basaran, S, Skovby, F, Hennekam, RC, Uzielli, ML, Schnur, RE, Manouvrier, S, Chang, S, Blair, E, Hurst, JA, Forzano, F, Meins, M, Simola, KO, Raas-Rothschild, A, Schultz, RA, McDaniel, LD, Ozono, K, Inui, K, Zou, H, Jabs, EW

Hum. Mol. Genet. 2008
18614053 Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast

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

Mol. Cell 2008
Participants
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Title
N-acetyltransferase activity of ESCO [nucleoplasm]
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Activity
Orthologous Events
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