The Cellular Response to Complex DNA Damage Induced by Ionising Radiation

Wilkinson, Beth, Hill, Mark AA and Parsons, Jason LL ORCID: 0000-0002-5052-1125 (2023) The Cellular Response to Complex DNA Damage Induced by Ionising Radiation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (5). 4920-.

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Official URL: http://dx.doi.org/10.3390/ijms24054920

Abstract

Radiotherapy (ionising radiation; IR) is utilised in the treatment of ~50% of all human cancers, and where the therapeutic effect is largely achieved through DNA damage induction. In particular, complex DNA damage (CDD) containing two or more lesions within one to two helical turns of the DNA is a signature of IR and contributes significantly to the cell killing effects due to the difficult nature of its repair by the cellular DNA repair machinery. The levels and complexity of CDD increase with increasing ionisation density (linear energy transfer, LET) of the IR, such that photon (X-ray) radiotherapy is deemed low-LET whereas some particle ions (such as carbon ions) are high-LET radiotherapy. Despite this knowledge, there are challenges in the detection and quantitative measurement of IR-induced CDD in cells and tissues. Furthermore, there are biological uncertainties with the specific DNA repair proteins and pathways, including components of DNA single and double strand break mechanisms, that are engaged in CDD repair, which very much depends on the radiation type and associated LET. However, there are promising signs that advancements are being made in these areas and which will enhance our understanding of the cellular response to CDD induced by IR. There is also evidence that targeting CDD repair, particularly through inhibitors against selected DNA repair enzymes, can exacerbate the impact of higher LET, which could be explored further in a translational context.

Item Type:	Article
Uncontrolled Keywords:	carbon ions, complex DNA damage, DNA repair, ionising radiation, linear energy transfer, proton beam therapy
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	19 Apr 2023 10:14
Last Modified:	05 Oct 2023 08:30
DOI:	10.3390/ijms24054920
Open Access URL:	https://doi.org/10.3390/ijms24054920
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3169736