Eukaryotic DNA polymerase ζ

Alena V Makarova1, Peter M Burgers2

  • 1Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA; Institute of Molecular Genetics, Russian Academy of Sciences (IMG RAS), Kurchatov Sq. 2, Moscow 123182, Russia.

DNA Repair
|March 5, 2015
PubMed

Insights

Eukaryotic DNA polymerase ζ (Pol ζ) drives mutagenesis during DNA damage and normal cell growth. Its four-subunit structure and interactions with Rev1 and PCNA, modulated by posttranslational modifications, are key to translesion synthesis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA polymerase ζ (Pol ζ) is central to eukaryotic mutagenesis.
  • It mediates mutations in response to DNA damage and during normal cell replication.
  • Understanding Pol ζ's structure and function is crucial for comprehending DNA repair and genomic stability.

Purpose of the Study:

  • To review recent advances in understanding the subunit structure of eukaryotic DNA polymerase ζ.
  • To explore the interactions of Pol ζ with other cellular factors like Rev1 and PCNA.
  • To highlight the role of posttranslational modifications in regulating Pol ζ activity.

Main Methods:

  • Review of existing literature on DNA polymerase ζ structure and function.
  • Analysis of research on protein-protein interactions involving Pol ζ.
  • Examination of studies on posttranslational modifications affecting Pol ζ activity.

Main Results:

  • Eukaryotic Pol ζ is a four-subunit complex involving shared subunits with DNA polymerase δ (Pol31, Pol32).
  • Pol ζ interacts with Rev1 and proliferating cell nuclear antigen (PCNA), which are essential for its mutagenic activity.
  • Posttranslational modifications, including ubiquitination and phosphorylation, regulate Pol ζ's role in translesion synthesis (TLS).

Conclusions:

  • The elucidated subunit structure of Pol ζ provides novel insights into its mutagenic mechanisms.
  • Interactions with Rev1 and PCNA, alongside posttranslational modifications, are critical for Pol ζ-mediated mutagenesis.
  • Further research into Pol ζ regulation could offer therapeutic targets for diseases involving DNA repair defects.

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