The Clustered DNA Lesions - Types, Pathways of Repair and Relevance to Human Health

Current Medicinal Chemistry
Barbara Bukowska, Boleslaw T Karwowski

Abstract

The clustered DNA lesions are a characteristic feature of ionizing radiation and are defined as two or more damage sites formed within 20 bps after the passage of a single radiation track. The clustered DNA lesions are divided into two major groups: double-stranded breaks (DSBs) and non-DSB clusters also known as Oxidatively-induced Clustered DNA Lesions (OCDLs), which could involve either two opposing strands or the same strand. As irradiation is gaining greater interest in cancer treatment as well as in imaging techniques, the detailed knowledge of its genotoxicity and the mechanisms of repair of radiation-induced DNA damage remain issues to explore. In this review we look at the ways the cell copes with clustered DNA lesions, especially with 5',8-cyclo-2'-deoxypurines. As the base excision repair deals with isolated lesions, complex damage is more difficult to repair. Depending on the number of lesions within a cluster, their types and mutual distribution, long-patch BER or NER are activated. During the repair of opposing lesions, DSBs could be generated, which are repaired either by nonhomologous end joining (NHEJ) or homologous recombination (HR). The repair of individual lesions within a cluster progresses gradually. This...Continue Reading

Citations

Jul 19, 2019·The British Journal of Radiology·Marco Durante, Silvia Formenti
Jun 4, 2020·Biomolecules·Bon Ham Yip
Jul 1, 2018·International Journal of Particle Therapy·Robert D Stewart
Aug 28, 2020·Frontiers in Genetics·Ilya O VelegzhaninovDmitry Yu Klokov
Aug 3, 2019·International Journal of Molecular Sciences·Yi Zheng, Léon Sanche
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Halil Ibrahim ToyAthanasia Pavlopoulou
Jun 22, 2021·Chemistry : a European Journal·Leander Simon RuntschThomas Carell
Aug 8, 2021·International Journal of Molecular Sciences·Yingxia GaoLéon Sanche
Nov 13, 2021·Photochemistry and Photobiology·Chaochao LiuLéon Sanche

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