title: Balancing repair and tolerance of DNA damage caused by alkylating agents.
abstract: 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.
authors.affiliation: Department of Biological Engineering, Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Dragony
authors.initials: D
authors.lastname: Fu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Calvo
authors.forename: Leona D
authors.initials: LD
authors.lastname: Samson
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D020137:Base Pair Mismatch; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans
chemical_list: D000477:Alkylating Agents