TY - JOUR
T1 - Removal of oxidatively generated DNA damage by overlapping repair pathways
AU - Shafirovich, Vladimir
AU - Geacintov, Nicholas E.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/6
Y1 - 2017/6
N2 - It is generally believed that the mammalian nucleotide excision repair pathway removes DNA helix-distorting bulky DNA lesions, while small non-bulky lesions are repaired by base excision repair (BER). However, recent work demonstrates that the oxidativly generated guanine oxidation products, spiroimininodihydantoin (Sp), 5-guanidinohydantoin (Gh), and certain intrastrand cross-linked lesions, are good substrates of NER and BER pathways that compete with one another in human cell extracts. The oxidation of guanine by peroxynitrite is known to generate 5-guanidino-4-nitroimidazole (NIm) which is structurally similar to Gh, except that the 4-nitro group in NIm is replaced by a keto group in Gh. However, unlike Gh, NIm is an excellent substrate of BER, but not of NER. These and other related results are reviewed and discussed in this article.
AB - It is generally believed that the mammalian nucleotide excision repair pathway removes DNA helix-distorting bulky DNA lesions, while small non-bulky lesions are repaired by base excision repair (BER). However, recent work demonstrates that the oxidativly generated guanine oxidation products, spiroimininodihydantoin (Sp), 5-guanidinohydantoin (Gh), and certain intrastrand cross-linked lesions, are good substrates of NER and BER pathways that compete with one another in human cell extracts. The oxidation of guanine by peroxynitrite is known to generate 5-guanidino-4-nitroimidazole (NIm) which is structurally similar to Gh, except that the 4-nitro group in NIm is replaced by a keto group in Gh. However, unlike Gh, NIm is an excellent substrate of BER, but not of NER. These and other related results are reviewed and discussed in this article.
KW - Base excision repair
KW - DNA damage
KW - Nucleotide excision repair
KW - Oxidative stress
KW - Reactive oxygen species
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U2 - 10.1016/j.freeradbiomed.2016.10.507
DO - 10.1016/j.freeradbiomed.2016.10.507
M3 - Review article
C2 - 27818219
AN - SCOPUS:85020010986
SN - 0891-5849
VL - 107
SP - 53
EP - 61
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -