TY - JOUR
T1 - A DNA oligomer containing 2,2,4-triamino-5(2H)-oxazolone is incised by human NEIL1 and NTH1
AU - Kino, Katsuhito
AU - Takao, Masashi
AU - Miyazawa, Hiroshi
AU - Hanaoka, Fumio
N1 - Funding Information:
Special thanks to Prof. A. Yasui from Tohoku University. This work was supported by research grants from Ministry of Education, Culture, Sports, Science and Technology of Japan , from Tokushima Bunri University and from the Japan Prize Foundation .
PY - 2012/6/1
Y1 - 2012/6/1
N2 - The nucleobase derivative, 2,2,4-triamino-5(2. H)-oxazolone (Oz), is an oxidation product of guanine or of 8-oxo-7,8-dihydroguanine that causes G-to-C transversions in DNA. Human NEIL1 (hNEIL1) and NTH1 (hNTH1) are homologues of two prokaryotic base excision repair enzymes, FPG/NEI and NTH, respectively. Here, we demonstrated that hNEIL1 and hNTH1 cleave Oz sites as efficiently as 5-hydroxyuracil sites. Thus, hNEIL1 and hNTH1 can repair Oz lesions. Furthermore, the nicking activities of these enzymes are largely independent of nucleobases opposite Oz; this finding indicates that removing Oz from Oz:G and Oz:A base pairs might cause an increase in the rate of point mutations in human cells.
AB - The nucleobase derivative, 2,2,4-triamino-5(2. H)-oxazolone (Oz), is an oxidation product of guanine or of 8-oxo-7,8-dihydroguanine that causes G-to-C transversions in DNA. Human NEIL1 (hNEIL1) and NTH1 (hNTH1) are homologues of two prokaryotic base excision repair enzymes, FPG/NEI and NTH, respectively. Here, we demonstrated that hNEIL1 and hNTH1 cleave Oz sites as efficiently as 5-hydroxyuracil sites. Thus, hNEIL1 and hNTH1 can repair Oz lesions. Furthermore, the nicking activities of these enzymes are largely independent of nucleobases opposite Oz; this finding indicates that removing Oz from Oz:G and Oz:A base pairs might cause an increase in the rate of point mutations in human cells.
KW - Base excision repair enzyme
KW - Guanine oxidation
KW - Human NEIL1
KW - Human NTH1
KW - Oxazolone
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U2 - 10.1016/j.mrfmmm.2012.03.007
DO - 10.1016/j.mrfmmm.2012.03.007
M3 - Article
C2 - 22465744
AN - SCOPUS:84862027113
VL - 734
SP - 73
EP - 77
JO - Mutation Research
JF - Mutation Research
SN - 0027-5107
IS - 1-2
ER -
