DNA Damage Tolerance in Stem Cells, Ageing, Mutagenesis, Disease and Cancer Therapy

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2019 Jun 29

PMID 31251805

Citations 39

Authors

Bas Pilzecker

Olimpia Alessandra Buoninfante

Heinz Jacobs

Affiliations

Soon will be listed here.

Abstract

The DNA damage response network guards the stability of the genome from a plethora of exogenous and endogenous insults. An essential feature of the DNA damage response network is its capacity to tolerate DNA damage and structural impediments during DNA synthesis. This capacity, referred to as DNA damage tolerance (DDT), contributes to replication fork progression and stability in the presence of blocking structures or DNA lesions. Defective DDT can lead to a prolonged fork arrest and eventually cumulate in a fork collapse that involves the formation of DNA double strand breaks. Four principal modes of DDT have been distinguished: translesion synthesis, fork reversal, template switching and repriming. All DDT modes warrant continuation of replication through bypassing the fork stalling impediment or repriming downstream of the impediment in combination with filling of the single-stranded DNA gaps. In this way, DDT prevents secondary DNA damage and critically contributes to genome stability and cellular fitness. DDT plays a key role in mutagenesis, stem cell maintenance, ageing and the prevention of cancer. This review provides an overview of the role of DDT in these aspects.

Citing Articles

Metabolic Rewiring in the Face of Genomic Assault: Integrating DNA Damage Response and Cellular Metabolism.

Ma W, Zhou S Biomolecules. 2025; 15(2).

PMID: 40001471 PMC: 11852599. DOI: 10.3390/biom15020168.

Molecular dependencies and genomic consequences of a global DNA damage tolerance defect.

de Groot D, Spanjaard A, Shah R, Kreft M, Morris B, Lieftink C Genome Biol. 2024; 25(1):323.

PMID: 39741332 PMC: 11687044. DOI: 10.1186/s13059-024-03451-z.

Rev7 promotes non-homologous end-joining by blocking Mre11 nuclease and Rad50's ATPase activities and homologous recombination.

Badugu S, Dhyani K, Thakur M, Muniyappa K Elife. 2024; 13.

PMID: 39630591 PMC: 11616998. DOI: 10.7554/eLife.96933.

REV1 coordinates a multi-faceted tolerance response to DNA alkylation damage and prevents chromosome shattering in Drosophila melanogaster.

Khodaverdian V, Sano T, Maggs L, Tomarchio G, Dias A, Tran M PLoS Genet. 2024; 20(7):e1011181.

PMID: 39074150 PMC: 11309488. DOI: 10.1371/journal.pgen.1011181.

Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair.

Shah R, Aslam M, Spanjaard A, de Groot D, Zurcher L, Altelaar M PNAS Nexus. 2024; 3(7):pgae242.

PMID: 38957451 PMC: 11217772. DOI: 10.1093/pnasnexus/pgae242.

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