TY - JOUR
T1 - Removal of oxidatively generated DNA damage by overlapping repair pathways
AU - Shafirovich, Vladimir
AU - Geacintov, Nicholas E.
N1 - Funding Information:
This work was supported by the National Institute of Environmental Health Sciences Grants R01 ES 027059 to VS and R01 ES024050 to NEG. Components of this work were conducted in the Shared Instrumentation Facility at NYU that was constructed with support from a Research Facilities Improvement Grant (C06 RR-16572) from the National Center for Research Resources, National Institutes of Health. The acquisition of the MALDI-TOF mass spectrometer was supported by the National Science Foundation (CHE-0958457).
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
UR - http://www.scopus.com/inward/record.url?scp=85020010986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020010986&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2016.10.507
DO - 10.1016/j.freeradbiomed.2016.10.507
M3 - Review article
C2 - 27818219
AN - SCOPUS:85020010986
VL - 107
SP - 53
EP - 61
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -