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DNA crosslinking and alkylation sites refer to chemical modifications of DNA, resulting from the covalent attachment of alkyl groups or crosslinking between DNA strands, or between DNA and proteins. These lesions are primarily formed by the action of chemotherapeutic agents such as alkylating agents or platinum-based drugs, which attack nucleophilic sites on DNA bases (especially guanine), leading to the formation of intra- or inter-strand crosslinks and monoadducts. Such lesions disrupt DNA replication and transcription, causing cell cycle arrest and eventually cell death. The induction of DNA crosslinking/alkylation is exploited therapeutically to kill rapidly dividing cancer cells, but also poses a risk to normal cells, leading to genotoxic side effects and elevated risk of secondary cancers. These sites are not molecular "targets" per se, but are the direct result of damage caused by pharmacological or environmental agents.
Covalent alkylation or crosslinking of DNA nucleotides, forming intra- or inter-strand links that prevent DNA unwinding, replication, and transcription, ultimately leading to cell cycle arrest and death
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