| Full Name | Establishment of Sister Chromatid Cohesion N-Acetyltransferase 2 |
|---|---|
| Symbol | ESCO2 |
| Chromosomal Location | 8q21.11 |
| NCBI Gene ID | [157570](https://www.ncbi.nlm.nih.gov/gene/157570) |
| OMIM | [609353](https://omim.org/entry/609353) |
| Ensembl ID | [ENSG00000174607](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000174607) |
| UniProt | [Q5ICG6](https://www.uniprot.org/uniprot/Q5ICG6) |
| Associated Diseases | [Roberts Syndrome](/roberts-syndrome), [SC Phocomelia](/sc-phocomelia), [Cohesinopathy](/cohesinopathy) |
ESCO2 (Establishment of Sister Chromatid Cohesion N-Acetyltransferase 2) is an S-phase specific lysine acetyltransferase that acetylates the SMC3 subunit of the cohesin complex, a modification essential for establishing sister chromatid cohesion during DNA replication. Mutations in ESCO2 cause Roberts syndrome (RBS), a severe autosomal recessive developmental disorder characterized by limb malformations, growth deficiency, and craniofacial abnormalities[1].
ESCO2 catalyzes the acetylation of SMC3 at lysine residues K105 and K106, which:
Unlike ESCO1 (constitutively active), ESCO2 functions specifically during DNA replication:
ESCO2 participates in genome maintenance:
Key differences between ESCO1 and ESCO2:
| Feature | ESCO1 | ESCO2 |
|---|---|---|
| Cell cycle | Constitutive | S-phase specific |
| Primary role | Maintenance cohesion | Establishment cohesion |
| Disease association | Cancer | Roberts syndrome |
| PCNA binding | No | Yes |
Biallelic ESCO2 mutations cause Roberts syndrome, characterized by:
Genetic features:
A milder allelic disorder caused by hypomorphic ESCO2 mutations:
While less commonly mutated than other cohesin components, ESCO2 alterations occur in:
ESCO2 expression is tightly cell cycle-regulated:
Highest expression in:
Low expression in post-mitotic neurons and quiescent tissues.
Current management is supportive:
Research directions include:
Vega H, et al. Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesion. Nature Genetics. 2005. ↩︎
Unal E, et al. A molecular determinant for the establishment of sister chromatid cohesion. Science. 2008. ↩︎
Terret ME, et al. Cohesin acetylation speeds the replication fork. Nature. 2009. ↩︎
Watrin E, Peters JM. The cohesin complex is required for the DNA damage-induced G2/M checkpoint. Molecular Cell. 2006. ↩︎
Gordillo M, et al. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity. Human Mutation. 2008. ↩︎
Schulz B, et al. ESCO2 deficiency and the Roberts syndrome phenotype. American Journal of Medical Genetics Part A. 2005. ↩︎
Hou F, Zou H. Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion. Molecular Biology of the Cell. 2005. ↩︎
van der Lelij P, et al. TOR signaling promotes sister chromatid cohesion. EMBO Journal. 2014. ↩︎