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CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during

Lise-Marie Donnio1, Anna Lagarou1, Gabrielle Sueur2

  • 1Institut NeuroMyoGène (INMG), CNRS UMR 5310, INSERM U1217, Université de Lyon, Université Claude Bernard Lyon 1, Villeurbanne, France.

Molecular and Cellular Biology
|January 4, 2019
PubMed

Insights

DNA repair allows transcription to restart after UV damage. Cockayne syndrome group B protein (CSB) is crucial for RNA polymerase II phosphorylation and transcription restart, while CDK9 plays a nonenzymatic role.

Area of Science:

  • Molecular Biology
  • DNA Repair Mechanisms
  • Gene Transcription Regulation

Background:

  • DNA damage, such as lesions, impedes cellular processes like transcription, potentially leading to apoptosis, tissue dysfunction, and premature aging.
  • Cells possess diverse DNA repair pathways, including transcription-coupled repair, which removes helix-distorting DNA adducts.
  • While DNA repair is well-studied, the subsequent process of transcription restart remains poorly understood.

Purpose of the Study:

  • To investigate the molecular mechanisms governing transcription restart following DNA repair after UV irradiation.
  • To elucidate the roles of specific proteins, including Cyclin-Dependent Kinase 9 (CDK9) and Cockayne Syndrome Group B protein (CSB), in this process.

Main Methods:

  • UV irradiation of cells to induce DNA damage.
  • Analysis of protein complex dynamics, specifically the release and degradation of the CDK9/cyclin T1 unit from HEXIM1.
  • Assessment of RNA polymerase II phosphorylation, particularly at the Ser2 position, and its dependence on CSB.
  • Investigating the enzymatic or nonenzymatic function of CDK9 in transcription restart.

Main Results:

  • UV irradiation triggers the specific release of the CDK9/cyclin T1 kinase unit from the HEXIM1 complex.
  • The released CDK9/cyclin T1 fraction undergoes degradation in cells lacking the Cockayne Syndrome Group B protein (CSB).
  • UV irradiation induces CSB-dependent Ser2 phosphorylation of RNA polymerase II, a modification critical for transcription restart.

Conclusions:

  • The Cockayne Syndrome Group B protein (CSB) is essential for the specific phosphorylation of RNA polymerase II following UV-induced DNA damage, facilitating transcription restart.
  • Cyclin-Dependent Kinase 9 (CDK9) appears to play a nonenzymatic role in transcription restart after DNA repair, rather than a direct enzymatic one in phosphorylation.
  • Understanding these mechanisms provides insight into cellular recovery from DNA damage and the regulation of gene expression.
Keywords:
CDK9DNA repairRNAP2nucleotide excision repairtranscriptiontranscription-coupled repair

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