Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities

Overview

Journal Trends Biochem Sci

Specialty Biochemistry

Date 2016 Nov 7

PMID 27816326

Citations 54

Authors

Jennifer M Soll

Robert W Sobol

Nima Mosammaparast

Affiliations

Soon will be listed here.

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.

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