Induction of DNA-protein cross-links by ionizing radiation and their elimination from the genome

Mutation Research
Toshiaki NakanoHiroshi Ide

Abstract

Ionizing radiation produces various types of DNA lesions, such as base damage, single-strand breaks, double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, DSBs are the most critical lesions underlying the lethal effects of ionizing radiation. With DPCs, proteins covalently trapped in DNA constitute strong roadblocks to replication and transcription machineries, and hence can be lethal to cells. The formation of DPCs by ionizing radiation is promoted in the absence of oxygen, whereas that of DSBs is retarded. Accordingly, the contribution of DPCs to the lethal events in irradiated cells may not be negligible for hypoxic cells, such as those present in tumors. However, the role of DPCs in the lethal effects of ionizing radiation remains largely equivocal. In the present study, normoxic and hypoxic mouse tumors were irradiated with X-rays [low linear energy transfer (LET) radiation] and carbon (C)-ion beams (high LET radiation), and the resulting induction of DPCs and DSBs and their removal from the genome were analyzed. X-rays and C-ion beams produced more DPCs in hypoxic tumors than in normoxic tumors. Interestingly, the yield of DPCs was slightly but statistically significantly greater (1.3- to 1.5-fold) fo...Continue Reading

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Citations

Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jason L QuiñonesBruce Demple
Oct 3, 2015·Radiation Research·Naoto ShimizuKouji Hirota
Nov 27, 2018·Journal of Radiation Research·Yoshihiko HagiwaraAtsushi Shibata
Aug 28, 2020·Frontiers in Genetics·Ilya O VelegzhaninovDmitry Yu Klokov
May 7, 2021·Biochimica Et Biophysica Acta. Proteins and Proteomics·Xiaoying WeiKun Yang

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