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Updated: Apr 16, 2026

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
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.
Abstract:
This review focuses on eukaryotic DNA polymerase ζ (Pol ζ), the enzyme responsible for the bulk of mutagenesis in eukaryotic cells in response to DNA damage. Pol ζ is also responsible for a large portion of mutagenesis during normal cell growth, in response to spontaneous damage or to certain DNA structures and other blocks that stall DNA replication forks. Novel insights in mutagenesis have been derived from recent advances in the elucidation of the subunit structure of Pol ζ. The lagging strand DNA polymerase δ shares the small Pol31 and Pol32 subunits with the Rev3-Rev7 core assembly giving a four subunit Pol ζ complex that is the active form in mutagenesis. Furthermore, Pol ζ forms essential interactions with the mutasome assembly factor Rev1 and with proliferating cell nuclear antigen (PCNA). These interactions are modulated by posttranslational modifications such as ubiquitination and phosphorylation that enhance translesion synthesis (TLS) and mutagenesis.
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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