Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities

Jennifer M. Soll, Robert W. Sobol, Nima Mosammaparast

Research output: Contribution to journalReview articlepeer-review

55 Scopus citations

Abstract

Alkylation chemotherapy is one of the most widely used systemic therapies for cancer. While somewhat effective, clinical responses and toxicities of these agents are highly variable. A major contributing factor for this variability is the numerous distinct lesions that are created upon alkylation damage. These adducts activate multiple repair pathways. There is mounting evidence that the individual pathways function cooperatively, suggesting that coordinated regulation of alkylation repair is critical to prevent toxicity. Furthermore, some alkylating agents produce adducts that overlap with newly discovered methylation marks, making it difficult to distinguish between bona fide damaged bases and so-called ‘epigenetic’ adducts. Here, we discuss new efforts aimed at deciphering the mechanisms that regulate these repair pathways, emphasizing their implications for cancer chemotherapy.

Original languageEnglish
Pages (from-to)206-218
Number of pages13
JournalTrends in biochemical sciences
Volume42
Issue number3
DOIs
StatePublished - Mar 1 2017

Keywords

  • AlkB
  • MGMT
  • alkylation chemotherapy
  • base excision repair

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