Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo
Toxicol. Res. 2018;34:297−302
Published online October 15, 2018;  https://doi.org/10.5487/TR.2018.34.4.297
© 2018 Korean Society of Toxicology.

Shingo Fujii1,2,3,4, Asako Isogawa1,2,3,4 and Robert P. Fuchs1,2,3,4

1DNA Damage Tolerance CNRS, UMR7258, Marseille, France
2Institut Paoli-Calmettes, Marseille, France
3Aix-Marseille University, UM 105, Marseille, France
4Inserm, U1068, CRCM, Marseille, France
Robert P. Fuchs, Inserm, U1068, CRCM, Marseille, 13009, France
E-mail: robert.fuchs@inserm.fr
Received: July 30, 2018; Revised: August 16, 2018; Accepted: August 30, 2018
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Cells are constantly exposed to endogenous and exogenous chemical and physical agents that damage their genome by forming DNA lesions. These lesions interfere with the normal functions of DNA such as transcription and replication, and need to be either repaired or tolerated. DNA lesions are accurately removed via various repair pathways. In contrast, tolerance mechanisms do not remove lesions but only allow replication to proceed despite the presence of unrepaired lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS), which is an error-prone strategy and an accurate strategy based on homologous recombination (homology-dependent gap repair [HDGR]). Thus, the mutation frequency reflects the relative extent to which the two tolerance pathways operate in vivo. In the present paper, we review the present understanding of the mechanisms of TLS and HDGR and propose a novel and comprehensive view of the way both strategies interact and are regulated in vivo.
Keywords : DNA damage tolerance, Translesion synthesis, Recombinational repair


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