How a Homolog of High-fidelity Replicases Conducts Mutagenic DNA Synthesis

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2015 Mar 17

PMID 25775266

Citations 29

Authors

Young-Sam Lee

Yang Gao

Wei Yang

Affiliations

Soon will be listed here.

Abstract

All DNA replicases achieve high fidelity by a conserved mechanism, but each translesion polymerase carries out mutagenic DNA synthesis in its own way. Here we report crystal structures of human DNA polymerase ν (Pol ν), which is homologous to high-fidelity replicases yet is error prone. Instead of a simple open-to-closed movement of the O helix upon binding of a correct incoming nucleotide, Pol ν has a different open state and requires the finger domain to swing sideways and undergo both opening and closing motions to accommodate the nascent base pair. A single-amino acid substitution in the O helix of the finger domain improves the fidelity of Pol ν nearly ten-fold. A unique cavity and the flexibility of the thumb domain allow Pol ν to generate and accommodate a looped-out primer strand. Primer loop-out may be a mechanism for DNA trinucloetide-repeat expansion.

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