TY - JOUR
T1 - The complexity and regulation of repair of alkylation damage to nucleic acids
AU - Tsao, Ning
AU - Schärer, Orlando D.
AU - Mosammaparast, Nima
N1 - Funding Information:
N. M. and O. D. S. are members of the Structural Cell Biology of DNA Repair program project [NIH P01 CA092584]. Work in the NM laboratory is supported the by the NIH [R01 CA193318 and R01 CA227001], the American Cancer Society research scholar program [RSG-18-156-01-DMC], and the Alvin J. Siteman Cancer Center Investment Program, which is supported by the Foundation for Barnes-Jewish Hospital Cancer Frontier Fund and the National Cancer Institute, Cancer Support Grant P30 CA091842. Work in the ODS laboratory is supported by the Korean Institute for Basic Science [IBS-R022-A1] and the NIH [R01 CA218315].
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - DNA damaging agents have been a cornerstone of cancer therapy for nearly a century. The discovery of many of these chemicals, particularly the alkylating agents, are deeply entwined with the development of poisonous materials originally intended for use in warfare. Over the last decades, their anti-proliferative effects have focused on the specific mechanisms by which they damage DNA, and the factors involved in the repair of such damage. Due to the variety of aberrant adducts created even for the simplest alkylating agents, numerous pathways of repair are engaged as a defense against this damage. More recent work has underscored the role of RNA damage in the cellular response to these agents, although the understanding of their role in relation to established DNA repair pathways is still in its infancy. In this review, we discuss the chemistry of alkylating agents, the numerous ways in which they damage nucleic acids, as well as the specific DNA and RNA repair pathways which are engaged to counter their effects.
AB - DNA damaging agents have been a cornerstone of cancer therapy for nearly a century. The discovery of many of these chemicals, particularly the alkylating agents, are deeply entwined with the development of poisonous materials originally intended for use in warfare. Over the last decades, their anti-proliferative effects have focused on the specific mechanisms by which they damage DNA, and the factors involved in the repair of such damage. Due to the variety of aberrant adducts created even for the simplest alkylating agents, numerous pathways of repair are engaged as a defense against this damage. More recent work has underscored the role of RNA damage in the cellular response to these agents, although the understanding of their role in relation to established DNA repair pathways is still in its infancy. In this review, we discuss the chemistry of alkylating agents, the numerous ways in which they damage nucleic acids, as well as the specific DNA and RNA repair pathways which are engaged to counter their effects.
KW - AlkB
KW - Alkylation
KW - DNA repair
KW - MGMT
KW - RNA damage
KW - base excision repair
KW - nucleotide excision repair
UR - http://www.scopus.com/inward/record.url?scp=85099339354&partnerID=8YFLogxK
U2 - 10.1080/10409238.2020.1869173
DO - 10.1080/10409238.2020.1869173
M3 - Review article
C2 - 33430640
AN - SCOPUS:85099339354
SN - 1040-9238
VL - 56
SP - 125
EP - 136
JO - Critical Reviews in Biochemistry and Molecular Biology
JF - Critical Reviews in Biochemistry and Molecular Biology
IS - 2
ER -