Why Do DNA Double Strand Breaks?

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DNA Double strand breaks (DSBs) are most toxic lesions and needs an immediate response from the cellular machinery. Ionizing radiation (IR), radiomimetic drugs (e.g. bleomycin and neocarzinostatin) and chemical agents such as poisons of DNA topoisomerases (e.g. camptothecin, etoposide and their derivatives ) are the major exogenous sources of DSBs. DSBs can be induced directly in all cell cycle by exposure to these agents. 97,154]. Endogenously generated reactive oxygen species, conversion of stalled replication forks or single-strand DNA nicks encountered by replication fork also result in DSB formation [155,156].
Failure to repair DSBs leads to genetic alterations including deletions, translocations, aberrant fusion, which enhance genome

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