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The cohesin modifier ESCO2 is stable during DNA replication.

Allison M Jevitt1, Brooke D Rankin2, Jingrong Chen1

  • 1Cell Cycle and Cancer Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.

Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology
|January 28, 2023
PubMed
Summary

Sister chromatid cohesion relies on the ESCO2 acetyltransferase. This study found that ESCO2 protein remains stable during DNA replication in both embryonic and somatic cells, challenging previous degradation theories.

Keywords:
Cell cycleChromosome cohesionDNA replicationE3 ubiquitin ligaseESCO2Xenopus laevis egg extract

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Sister chromatid cohesion, mediated by the cohesin complex, is crucial for accurate chromosome segregation and DNA repair.
  • ESCO2 acetyltransferase promotes cohesion by acetylating SMC3, preventing cohesin release.
  • ESCO2 interacts with DNA replication machinery via PCNA-interacting protein (PIP) motifs.

Purpose of the Study:

  • To investigate the stability of ESCO2 protein during DNA replication.
  • To determine if Cul4-dependent degradation regulates ESCO2 levels post-replication.
  • To validate ESCO2 stability in both cell-free and cellular systems.

Main Methods:

  • Characterization of ESCO2 stability in Xenopus egg extracts (cell-free system).
  • Assessment of ESCO2 stability under conditions of induced DNA damage and increased replication.
  • Analysis of GFP-ESCO2 stability in transgenic somatic cell lines using flow cytometry and live-cell imaging.

Main Results:

  • ESCO2 protein demonstrated stability throughout DNA replication in Xenopus egg extracts.
  • Neither DNA damage signaling nor increased replication load significantly impacted ESCO2 stability.
  • No evidence of GFP-ESCO2 degradation was observed during the S phase in transgenic somatic cells.

Conclusions:

  • ESCO2 protein is stable during the S phase of the cell cycle in both embryonic and somatic cells.
  • The proposed Cul4-dependent degradation of ESCO2 following replication may not be a primary regulatory mechanism in these systems.
  • ESCO2 stability is maintained irrespective of replication stress or DNA damage signaling during S phase.