Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Aug 26, 2015; 6(3): 48-56
Published online Aug 26, 2015. doi: 10.4331/wjbc.v6.i3.48
Mechanism of DNA damage tolerance
Xin Bi
Xin Bi, Department of Biology, University of Rochester, Rochester, NY 14627, United States
Author contributions: Bi X solely contributed to this paper.
Supported by United States National Science Foundation, No. MCB-1158008.
Conflict-of-interest statement: Xin Bi declares that no conflict of interest exists.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xin Bi, PhD, Professor, Department of Biology, University of Rochester, Rochester, NY 14627, United States. xin.bi@rochester.edu
Telephone: +1-585-2756922 Fax: +1-585-2752070
Received: March 3, 2015
Peer-review started: March 3, 2015
First decision: May 13, 2015
Revised: June 4, 2015
Accepted: July 29, 2015
Article in press: August 3, 2015
Published online: August 26, 2015
Abstract

DNA damage may compromise genome integrity and lead to cell death. Cells have evolved a variety of processes to respond to DNA damage including damage repair and tolerance mechanisms, as well as damage checkpoints. The DNA damage tolerance (DDT) pathway promotes the bypass of single-stranded DNA lesions encountered by DNA polymerases during DNA replication. This prevents the stalling of DNA replication. Two mechanistically distinct DDT branches have been characterized. One is translesion synthesis (TLS) in which a replicative DNA polymerase is temporarily replaced by a specialized TLS polymerase that has the ability to replicate across DNA lesions. TLS is mechanistically simple and straightforward, but it is intrinsically error-prone. The other is the error-free template switching (TS) mechanism in which the stalled nascent strand switches from the damaged template to the undamaged newly synthesized sister strand for extension past the lesion. Error-free TS is a complex but preferable process for bypassing DNA lesions. However, our current understanding of this pathway is sketchy. An increasing number of factors are being found to participate or regulate this important mechanism, which is the focus of this editorial.

Keywords: DNA damage tolerance, Template switching, DNA damage bypass, DNA replication, Replicative stress, Translesion synthesis, Ubiquitination, Sumoylation

Core tip: DNA damage may compromise genome integrity and lead to cell death. Cells have evolved a variety of processes to respond to DNA damage including damage repair and tolerance mechanisms. The DNA damage tolerance (DDT) pathway promotes the bypass of single-stranded DNA lesions encountered by DNA polymerases during DNA replication. This prevents the stalling of DNA replication. Two mechanistically distinct DDT branches, translesion synthesis and template switching have been characterized. However, our current understanding of DDT is far from complete and that of template switching is especially sketchy. This editorial focuses on recently identified components and regulators of DDT.