MutY is down-regulated by oxidative stress in E. coli.
In Escherichia coli, MutM (8-oxoG DNA glycosylase/lyase or Fpg protein), MutY (adenine DNA glycosylase) and MutT (8-oxodGTPase) function cooperatively to prevent mutation due to 7, 8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic oxidative DNA adduct. MutM activity has been demonstrated to be induced by oxidative stress. Its regulation is under the negative control of the global regulatory genes, fur, fnr and arcA. However, interestingly the presence of MutY increases the mutation frequency in mutT- background because of MutY removes adenine (A) from 8-oxoG:A which arises from the misincorporation of 8-oxoG against A during DNA replication. Accordingly we hypothesized that the response of MutY to oxidative stress is opposite to that of MutM and compared the regulation of MutY activity with MutM under various oxidative stimuli. Unlike MutM, MutY activity was reduced by oxidative stress. Its activity was reduced to 30% of that of the control when E. coli was treated with paraquat (0.5mM) or H2O2 (0.1 mM) and induced under anaerobic conditions to more than twice that observed under aerobic conditions. The reduced mRNA level of MutY coincided with its reduced activity by paraquat treatment. Also, the increased activity of MutY in anaerobic conditions was reduced further in E. coli strains with mutations in fur, fnr and arcA and the maximum reduction in activity was when all mutations were present in combination, indicating that MutY is under the positive control of these regulatory genes. Therefore, the down-regulation of MutY suggests that there has been complementary mechanism for its mutagenic activity under special conditions. Moreover, the efficacy of anti-mutagenic action should be enhanced by the reciprocal co-regulation of MutM.
Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, South Korea.
Sun-Hee
SH
Yoon
Hye-Sook
HS
Lee
Jeong-Yun
JY
Choi
Hee-Kyoung
HK
Kang
Jung-Jin
JJ
Lee
Jin-Won
JW
Hyun
Jinhee
J
Choi
Sang-Kyu
SK
Ye
Myung-Hee
MH
Chung
D004247:DNA / Q000737:chemistry / Q000378:metabolism; D045647:DNA Glycosylases / Q000096:biosynthesis*; D015536:Down-Regulation; D004926:Escherichia coli / Q000378:metabolism*; D008954:Models, Biological; D009153:Mutagens; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009153:Mutagens; D004247:DNA; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D010100:Oxygen