TY - JOUR
T1 - Regulation of DNA Alkylation Damage Repair
T2 - Lessons and Therapeutic Opportunities
AU - Soll, Jennifer M.
AU - Sobol, Robert W.
AU - Mosammaparast, Nima
N1 - Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - AlkB
KW - MGMT
KW - alkylation chemotherapy
KW - base excision repair
UR - http://www.scopus.com/inward/record.url?scp=85005808085&partnerID=8YFLogxK
U2 - 10.1016/j.tibs.2016.10.001
DO - 10.1016/j.tibs.2016.10.001
M3 - Review article
C2 - 27816326
AN - SCOPUS:85005808085
SN - 0968-0004
VL - 42
SP - 206
EP - 218
JO - Trends in biochemical sciences
JF - Trends in biochemical sciences
IS - 3
ER -