Selective inhibition by harmane of the apurinic apyrimidinic endonuclease activity of phage T4-induced UV endonuclease.
1-Methyl-9H-pyrido-[3,4-b]indole (harmane) inhibits the apurinic/apyrimidinic (AP) endonuclease activity of the UV endonuclease induced by phage T4, whereas it stimulates the pyrimidine dimer-DNA glycosylase activity of that enzyme. E. coli endonuclease IV, E. coli endonuclease VI (the AP endonuclease activity associated with E. coli exonuclease III), and E. coli uracil-DNA glycosylase were not inhibited by harmane. Human fibroblast AP endonucleases I and II also were only slightly inhibited. Therefore, harmane is neither a general inhibitor of AP endonucleases, nor a general inhibitor of Class I AP endonucleases which incise DNA on the 3'-side of AP sites. However, E. coli endonuclease III and its associated dihydroxythymine-DNA glycosylase activity were both inhibited by harmane. This observation suggests that harmane may inhibit only AP endonucleases which have associated glycosylase activities.
D000470:Alkaloids / Q000494:pharmacology*; D004279:DNA, Viral / Q000528:radiation effects; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043224:Deoxyribonuclease (Pyrimidine Dimer); D043223:Deoxyribonuclease IV (Phage T4-Induced); D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004706:Endodeoxyribonucleases; D004720:Endonucleases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins; D005347:Fibroblasts / Q000201:enzymology; D006247:Harmine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases; D013045:Species Specificity; D013604:T-Phages / Q000201:enzymology*; D014466:Ultraviolet Rays
D000470:Alkaloids; D004279:DNA, Viral; D029968:Escherichia coli Proteins; D009097:Multienzyme Complexes; D006247:Harmine; C032219:UV endonuclease; C005010:harman; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; D004720:Endonucleases; D043223:Deoxyribonuclease IV (Phage T4-Induced); C468972:endonuclease IV, E coli; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli; D009699:N-Glycosyl Hydrolases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase