Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.
Nat Struct Mol Biol
; 27(10): 913-924, 2020 10.
Article
de En
| MEDLINE
| ID: mdl-32807989
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéines de Saccharomyces cerevisiae
/
Réparation de l'ADN
Langue:
En
Journal:
Nat Struct Mol Biol
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2020
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique