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PCNA-Dependent Cleavage and Degradation of SDE2 Regulates Response to Replication Stress

Ukhyun Jo1, Winson Cai1, Jingming Wang1

  • 1Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.

Plos Genetics
|December 2, 2016
PubMed

Insights

Scientists discovered SDE2, a new genome surveillance factor. It regulates DNA replication and repair by interacting with Proliferating Cell Nuclear Antigen (PCNA), protecting cells from replication stress and genomic instability.

Area of Science:

  • Molecular Biology
  • Genomics
  • Cell Biology

Background:

  • Genomic integrity is crucial for cell survival and preventing cancer.
  • Proliferating Cell Nuclear Antigen (PCNA) is vital for DNA replication and recruits repair factors.
  • Posttranslational modification of PCNA coordinates DNA repair and cell cycle control.

Purpose of the Study:

  • Identify new genome surveillance factors.
  • Investigate the role of SDE2 in DNA replication and repair.
  • Elucidate the mechanism of SDE2 regulation by PCNA.

Main Methods:

  • Protein interaction studies
  • Ubiquitin-like (UBL) domain analysis
  • Ubiquitin E3 ligase assays (CRL4CDT2)
  • Cell cycle analysis
  • DNA damage response assays

Main Results:

  • Human SDE2 identified as a novel PCNA-interacting protein.
  • Cleaved SDE2 negatively regulates PCNA monoubiquitination and counteracts replication stress.
  • CRL4CDT2-mediated degradation of SDE2 is essential for cell cycle progression and survival.
  • Failure to degrade SDE2 impairs S phase progression and cellular survival.

Conclusions:

  • SDE2 acts as a genome surveillance factor regulated by PCNA.
  • Regulated proteolysis of SDE2 by CRL4CDT2 protects genomic integrity against replication stress.
  • An integrated UBL domain in SDE2 controls protein stability and function.

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