SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation

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Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae
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Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

Stine Jørgensen1, Morten Eskildsen, Kasper Fugger

  • 1Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.

The Journal of Cell Biology
|January 12, 2011
PubMed

Insights

The cell cycle regulator SET8 is degraded during S phase by the CRL4(CDT2) ubiquitin ligase and proliferating cell nuclear antigen (PCNA). This degradation controls chromatin compaction and cell cycle progression, especially after DNA damage.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The eukaryotic cell cycle involves ubiquitin-mediated events for regulating key proteins.
  • Histone H4 methyltransferase SET8 (Pr-Set7) is crucial for chromosome compaction and genome integrity.

Purpose of the Study:

  • To investigate the regulatory mechanism controlling SET8 levels during the cell cycle.
  • To determine the role of ubiquitylation in SET8 regulation and its impact on cell proliferation.

Main Methods:

  • Utilized techniques to study protein degradation pathways.
  • Investigated the interaction between SET8, CRL4(CDT2) ubiquitin ligase, and proliferating cell nuclear antigen (PCNA).
  • Analyzed SET8 ubiquitylation and degradation in response to cell cycle progression and DNA damage.

Main Results:

  • SET8 is degraded during S phase via the CRL4(CDT2) ubiquitin ligase in a PCNA-dependent manner.
  • A specific degron in SET8 mediates its interaction with PCNA and recruitment to chromatin for ubiquitylation.
  • SET8 degradation is essential for proper chromatin compaction and cell cycle progression.
  • SET8 turnover is enhanced after UV irradiation, involving CRL4(CDT2) and PCNA, aiding chromatin structure modulation post-DNA damage.

Conclusions:

  • Established a novel mechanism linking the ubiquitin-proteasome system to the rapid degradation of a histone methyltransferase (SET8).
  • Demonstrated that SET8 degradation is a critical regulatory step for controlling cell proliferation and chromatin dynamics.
  • Highlighted the role of SET8 turnover in responding to DNA damage and maintaining genome stability.

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