Balancing repair and tolerance of DNA damage caused by alkylating agents
Author(s)Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D.
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Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Center for Environmental Health Sciences; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology
Nature Reviews Cancer
Nature Publishing Group
Fu, Dragony, Jennifer A. Calvo, and Leona D. Samson. “Balancing Repair and Tolerance of DNA Damage Caused by Alkylating Agents.” Nature Reviews Cancer (January 12, 2012).
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