Eukaryotic DNA polymerase ζ.
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.
Department 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.
Alena V
AV
Makarova
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: burgers@biochem.wustl.edu.
Peter M
PM
Burgers
D004249:DNA Damage; D004258:DNA Polymerase III / Q000378:metabolism; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D056890:Eukaryota / Q000201:enzymology*; D006801:Humans; D016296:Mutagenesis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D004271:DNA, Fungal; D018809:Proliferating Cell Nuclear Antigen; C425929:DNA polymerase zeta; D004258:DNA Polymerase III; D004259:DNA-Directed DNA Polymerase
DNA polymerase; Mutagenesis; PCNA; Translesion synthesis