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[@vega2005].
Function
SMC3 Acetylation
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ESCO2 - Establishment of Sister Chromatid Cohesion N-Acetyltransferase 2
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[@vega2005].
Function
SMC3 Acetylation
ESCO2 catalyzes the acetylation of SMC3 at lysine residues K105 and K106, which:
Establishes cohesion: Creates stable sister chromatid linkages during S phase
Prevents premature separation: Protects cohesin from WAPL-mediated release
Ensures faithful segregation: Enables accurate chromosome distribution at anaphase[@unal2008]
Replication-Coupled Cohesion
Unlike ESCO1 (constitutively active), ESCO2 functions specifically during DNA replication:
Associates with the replication fork machinery
Couples cohesion establishment to DNA synthesis
Requires PCNA interaction for proper function[@terret2009]
DNA Damage Response
ESCO2 participates in genome maintenance:
Recruit to DNA double-strand breaks
Facilitates cohesion-mediated repair
Coordinates with BRCA1 and FANCD2[@watrin2006]
Distinct from ESCO1
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 |
Disease Associations
Roberts Syndrome (RBS)
Biallelic ESCO2 mutations cause Roberts syndrome, characterized by:
Prenatal growth deficiency: Severe growth restriction beginning in utero
Limb reductions: Tetraphocomelia (severe limb shortening) or milder limb defects
[NORD: Roberts Syndrome](https://rarediseases.org/rare-diseases/roberts-syndrome/)
References
[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 (2005)](https://doi.org/10.1038/ng1548)
[Unal E, et al, A molecular determinant for the establishment of sister chromatid cohesion (2008)](https://doi.org/10.1126/science.1157880)
[Terret ME, et al, Cohesin acetylation speeds the replication fork (2009)](https://doi.org/10.1038/nature08511)
[Watrin E, Peters JM, The cohesin complex is required for the DNA damage-induced G2/M checkpoint (2006)](https://doi.org/10.1016/j.molcel.2006.07.018)
[Gordillo M, et al, The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity (2008)](https://doi.org/10.1002/humu.20701)
[Schulz B, et al, ESCO2 deficiency and the Roberts syndrome phenotype (2005)](https://doi.org/10.1002/ajmg.a.30894)
[Hou F, Zou H, Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion (2005)](https://doi.org/10.1091/mbc.e05-04-0354)
[van der Lelij P, et al, TOR signaling promotes sister chromatid cohesion (2014)](https://doi.org/10.15252/embj.201488504)