Open AccessStructure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis
Author(s) -
Radhika Malik,
Mykhailo Kopylov,
Yacob Gómez-Llorente,
Rinku Jain,
Robert E. Johnson,
Louise Prakash,
Satya Prakash,
Iban Ubarretxena-Belandia,
Aneel K. Aggarwal
Publication year - 2020
Publication title -
nature structural and molecular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.448
H-Index - 270
eISSN - 1545-9993
pISSN - 1545-9985
DOI - 10.1038/s41594-020-0476-7
Subject(s) - dna polymerase , dna clamp , biology , dna polymerase ii , polymerase , dna replication , dna , dna polymerase delta , dna synthesis , dna damage , microbiology and biotechnology , genetics , gene , polymerase chain reaction , reverse transcriptase
DNA polymerase ζ (Polζ) belongs to the same B-family as high-fidelity replicative polymerases, yet is specialized for the extension reaction in translesion DNA synthesis (TLS). Despite its importance in TLS, the structure of Polζ is unknown. We present cryo-EM structures of the Saccharomyces cerevisiae Polζ holoenzyme in the act of DNA synthesis (3.1 Å) and without DNA (4.1 Å). Polζ displays a pentameric ring-like architecture, with catalytic Rev3, accessory Pol31' Pol32 and two Rev7 subunits forming an uninterrupted daisy chain of protein-protein interactions. We also uncover the features that impose high fidelity during the nucleotide-incorporation step and those that accommodate mismatches and lesions during the extension reaction. Collectively, we decrypt the molecular underpinnings of Polζ's role in TLS and provide a framework for new cancer therapeutics.