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Bulky Adducts in Clustered DNA Lesions: Causes of Resistance to the NER System

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Journal Acta Naturae
Specialty Biology
Date 2023 Jan 25
PMID 36694906
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Abstract

The nucleotide excision repair (NER) system removes a wide range of bulky DNA lesions that cause significant distortions of the regular double helix structure. These lesions, mainly bulky covalent DNA adducts, are induced by ultraviolet and ionizing radiation or the interaction between exogenous/endogenous chemically active substances and nitrogenous DNA bases. As the number of DNA lesions increases, e.g., due to intensive chemotherapy and combination therapy of various diseases or DNA repair impairment, clustered lesions containing bulky adducts may occur. Clustered lesions are two or more lesions located within one or two turns of the DNA helix. Despite the fact that repair of single DNA lesions by the NER system in eukaryotic cells has been studied quite thoroughly, the repair mechanism of these lesions in clusters remains obscure. Identification of the structural features of the DNA regions containing irreparable clustered lesions is of considerable interest, in particular due to a relationship between the efficiency of some antitumor drugs and the activity of cellular repair systems. In this review, we analyzed data on the induction of clustered lesions containing bulky adducts, the potential biological significance of these lesions, and methods for quantification of DNA lesions and considered the causes for the inhibition of NER-catalyzed excision of clustered bulky lesions.

References
1.
Falk M, Lukasova E, Kozubek S . Chromatin structure influences the sensitivity of DNA to gamma-radiation. Biochim Biophys Acta. 2008; 1783(12):2398-414. DOI: 10.1016/j.bbamcr.2008.07.010. View

2.
Gong J, Vaidyanathan V, Yu X, Kensler T, Peterson L, Sturla S . Depurinating acylfulvene-DNA adducts: characterizing cellular chemical reactions of a selective antitumor agent. J Am Chem Soc. 2007; 129(7):2101-11. DOI: 10.1021/ja0665951. View

3.
Buss P, Caviezel M, Lutz W . Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to aflatoxin B1. Carcinogenesis. 1990; 11(12):2133-5. DOI: 10.1093/carcin/11.12.2133. View

4.
Baker D, Wuenschell G, Xia L, Termini J, Bates S, Riggs A . Nucleotide excision repair eliminates unique DNA-protein cross-links from mammalian cells. J Biol Chem. 2007; 282(31):22592-604. DOI: 10.1074/jbc.M702856200. View

5.
Scharer O . Chemistry and biology of DNA repair. Angew Chem Int Ed Engl. 2003; 42(26):2946-74. DOI: 10.1002/anie.200200523. View