Eukaryotic translesion synthesis: Choosing the right tool for the job

Kyle T Powers; M Todd Washington

doi:10.1016/j.dnarep.2018.08.016

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Eukaryotic translesion synthesis: Choosing the right tool for the job

Journal article

Peer reviewed

Eukaryotic translesion synthesis: Choosing the right tool for the job

Kyle T Powers and M Todd Washington

DNA repair, Vol.71, pp.127-134

11/2018

DOI: 10.1016/j.dnarep.2018.08.016

PMCID: PMC6340752

PMID: 30174299

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https://www.ncbi.nlm.nih.gov/pmc/articles/6340752View

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Abstract

Normal DNA replication is blocked by DNA damage in the template strand. Translesion synthesis is a major pathway for overcoming these replication blocks. In this process, multiple non-classical DNA polymerases are thought to form a complex at the stalled replication fork that we refer to as the mutasome. This hypothetical multi-protein complex is structurally organized by the replication accessory factor PCNA and the non-classical polymerase Rev1. One of the non-classical polymerases within this complex then catalyzes replication through the damage. Each non-classical polymerase has one or more cognate lesions, which the enzyme bypasses with high accuracy and efficiency. Thus, the accuracy and efficiency of translesion synthesis depends on which non-classical polymerase is chosen to bypass the damage. In this review article, we discuss how the most appropriate polymerase is chosen. In so doing, we examine the structural motifs that mediate the protein interactions in the mutasome; the multiple architectures that the mutasome can adopt, such as PCNA tool belts and Rev1 bridges; the intrinsically disordered regions that tether the polymerases to PCNA and to one another; and the kinetic selection model in which the most appropriate polymerase is chosen via a competition among the multiple polymerases within the mutasome.

Saccharomyces cerevisiae - genetics

Humans

DNA Replication

DNA - metabolism

Eukaryota - metabolism

Saccharomyces cerevisiae - metabolism

Animals

Eukaryota - genetics

DNA Repair

Saccharomyces cerevisiae - enzymology

DNA Damage

DNA-Directed DNA Polymerase - metabolism

Eukaryota - enzymology

Proliferating Cell Nuclear Antigen - metabolism

Details

Title: Subtitle: Eukaryotic translesion synthesis: Choosing the right tool for the job
Creators: Kyle T Powers - Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242-1109, United States
M Todd Washington - Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242-1109, United States. Electronic address: todd-washington@uiowa.edu
Resource Type: Journal article
Publication Details: DNA repair, Vol.71, pp.127-134
DOI: 10.1016/j.dnarep.2018.08.016
PMID: 30174299
PMCID: PMC6340752
NLM abbreviation: DNA Repair (Amst)
ISSN: 1568-7864
eISSN: 1568-7856
Publisher: Netherlands
Grant note: R01 GM081433 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 11/2018
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984024403602771

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