ESCO1 - Establishment of Sister Chromatid Cohesion N-Acetyltransferase 1

ESCO1 - Establishment of Sister Chromatid Cohesion N-Acetyltransferase 1

<div class="infobox infobox-gene">
<h3>ESCO1</h3>
<table>
<tr><th>Full Name</th><td>Establishment of Sister Chromatid Cohesion N-Acetyltransferase 1</td></tr>
<tr><th>Symbol</th><td>ESCO1</td></tr>
<tr><th>Chromosomal Location</th><td>18q11.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[54970](https://www.ncbi.nlm.nih.gov/gene/54970)</td></tr>
<tr><th>OMIM</th><td>[609673](https://omim.org/entry/609673)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000131931](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000131931)</td></tr>
<tr><th>UniProt</th><td>[Q5F2C3](https://www.uniprot.org/uniprot/Q5F2C3)</td></tr>
<tr><th>Associated Diseases</th><td>[Bladder Cancer](/bladder-cancer), [Acute Myeloid Leukemia](/acute-myeloid-leukemia), [Cohesinopathy](/cohesinopathy)</td></tr>
</table>
</div>

Overview

ESCO1 (Establishment of Sister Chromatid Cohesion N-Acetyltransferase 1) is a lysine acetyltransferase that modifies the SMC3 subunit of the cohesin complex, a critical step in establishing sister chromatid cohesion during DNA replication. Together with its paralog ESCO2, ESCO1 regulates chromosome segregation, DNA repair, and gene expression programs essential for genomic stability and cellular function[@rolef2008].

Function

SMC3 Acetylation

ESCO1 - Establishment of Sister Chromatid Cohesion N-Acetyltransferase 1

<div class="infobox infobox-gene">
<h3>ESCO1</h3>
<table>
<tr><th>Full Name</th><td>Establishment of Sister Chromatid Cohesion N-Acetyltransferase 1</td></tr>
<tr><th>Symbol</th><td>ESCO1</td></tr>
<tr><th>Chromosomal Location</th><td>18q11.2</td></tr>
<tr><th>NCBI Gene ID</th><td>[54970](https://www.ncbi.nlm.nih.gov/gene/54970)</td></tr>
<tr><th>OMIM</th><td>[609673](https://omim.org/entry/609673)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000131931](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000131931)</td></tr>
<tr><th>UniProt</th><td>[Q5F2C3](https://www.uniprot.org/uniprot/Q5F2C3)</td></tr>
<tr><th>Associated Diseases</th><td>[Bladder Cancer](/bladder-cancer), [Acute Myeloid Leukemia](/acute-myeloid-leukemia), [Cohesinopathy](/cohesinopathy)</td></tr>
</table>
</div>

Overview

ESCO1 (Establishment of Sister Chromatid Cohesion N-Acetyltransferase 1) is a lysine acetyltransferase that modifies the SMC3 subunit of the cohesin complex, a critical step in establishing sister chromatid cohesion during DNA replication. Together with its paralog ESCO2, ESCO1 regulates chromosome segregation, DNA repair, and gene expression programs essential for genomic stability and cellular function[@rolef2008].

Function

SMC3 Acetylation

ESCO1 catalyzes the acetylation of two evolutionarily conserved lysine residues on SMC3 (K105 and K106 in humans), which:

• Stabilizes cohesive interactions: Locks cohesin onto chromatin to maintain sister chromatid cohesion
• Protects from WAPL-mediated release: Prevents premature cohesin unloading
• Establishes functional cohesin: Generates the cohesin form competent for S phase functions[@unal2008]

Cell Cycle Regulation

ESCO1 and ESCO2 have partially redundant but distinct roles:

• ESCO1: Constitutively expressed, acetylates cohesin throughout the cell cycle, involved in DNA damage response
• ESCO2: S-phase specific, critical for replication-coupled cohesion establishment[@alomer2017]

DNA Damage Response

ESCO1 contributes to genome maintenance by:

• Acetylating cohesin at DNA double-strand breaks
• Facilitating homologous recombination repair
• Coordinating checkpoint signaling[@watrin2006]

Gene Regulation

Beyond cohesion, ESCO1-mediated acetylation influences:

• Chromatin accessibility at enhancer regions
• Transcriptional elongation
• Three-dimensional genome organization[@merkenschlager2013]

Disease Associations

Cancer

ESCO1 alterations occur in several malignancies:

Bladder Cancer: ESCO1 mutations and downregulation correlate with:

• Tumor progression
• Poor prognosis
• Genomic instability phenotypes[@rieger2019]

• Leukemogenesis
• Altered differentiation programs
• Therapeutic vulnerabilities[@kon2013]

• Chromosomal instability
• Treatment resistance

Developmental Disorders

While ESCO2 mutations cause Roberts syndrome, ESCO1 variants have been implicated in:

• Milder developmental phenotypes
• Combined ESCO1/ESCO2 deficiencies causing severe cohesion defects

Expression

ESCO1 shows ubiquitous expression with relative enrichment in:

• Proliferating cell populations
• Bone marrow
• Lymphoid tissues
• Developing embryo[@zhang2019]

Allen Brain Atlas Data

Moderate expression throughout the brain, with slightly higher levels in:

• Neurogenic regions
• Actively dividing neural progenitors

Therapeutic Implications

Cancer Therapeutics

ESCO1 and cohesin represent potential therapeutic targets:

• Synthetic lethality: PARP inhibitors may be effective in ESCO1-deficient tumors
• Combination strategies: With DNA damage response inhibitors
• Biomarker potential: ESCO1 status may predict treatment response[@mondal2020]

Chromosomal Instability

Targeting ESCO1-mediated cohesion could exploit:

• Cancer cell replication stress
• Chromosome segregation vulnerabilities

See Also

• [ESCO2](/genes/esco2) - Paralog, Roberts syndrome gene](/genes)
• [SMC3](/genes/smc3) - Acetylation substrate](/genes)
• [SMC1A](/genes/smc1a) - Cohesin complex partner](/genes)
• [RAD21](/genes/rad21) - Cohesin ring component](/genes)
• [NIPBL](/genes/nipbl) - Cohesin loader](/genes)
• [WAPL](/wapl) - Cohesin release factor
• [Cohesin Complex](/cohesin-complex) - Mechanism page

External Links

• [GeneCards: ESCO1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ESCO1)
• [UniProt: Q5F2C3](https://www.uniprot.org/uniprot/Q5F2C3)
• [Human Protein Atlas: ESCO1](https://www.proteinatlas.org/ENSG00000131931-ESCO1)

References