Kayayyaki

Lalacewar Oxidative ga tushen DNA yawanci yana haifar da samuwar purines oxidized, musamman 7,8-dihydro-8-oxoguanine (8-oxoG) da 7,8-dihydro-8-oxoadenine (8-oxoA), tsohon kasancewa mai kyau- sananne mutagenic rauni.Tun da 8-oxoG yana cikin shirye-shiryen batun ƙara iskar oxygen idan aka kwatanta da sansanonin al'ada, an bincika shigar da tushe yayin haɗin DNA sabanin nau'in oxidized na 8-oxoG a cikin vitro.Samfurin roba wanda ke dauke da raunin 8-oxoG guda daya an fara bi da shi tare da nau'ikan oxidants na lantarki daban-daban ko kuma ƙarƙashin yanayin oxygen guda ɗaya sannan kuma an ƙaddamar da ƙarin haɓakawa ta hanyar Klenow fragment exo- (Kf exo-), calf thymus DNA polymerase alpha (pol alpha). ) ko DNA polymerase beta (pol beta).Daidai da rahotannin da suka gabata, an saka dAMP da dCMP tare da zaɓin sabanin 8-oxoG tare da duk polymerases na DNA guda uku.Abin sha'awa, an samo iskar oxygen ta 8-oxoG don haifar da shigar dAMP da dGMP gabanin raunin ta Kf exo- tare da hana wuce gona da iri na tsawaita al'ada o yana faruwa a wurin da aka gyara.Bugu da ƙari kuma, raunin ya zama toshe yayin haɗin DNA ta hanyar pol alpha da pol beta.Gwaje-gwaje tare da samfurin 8-oxoA-gyara oligonucleotide sun nuna cewa duka 8-oxoA da nau'in oxidized na 8-oxoA shigar da dTMP kai tsaye ta Kf exo-.Mass spectrometric analysis of 8-oxoG-dauke da oligonucleotides kafin da kuma bayan hadawan abu da iskar shaka tare da IrCl62-sun yi daidai da hadawan abu da iskar shaka na farko da 8-oxoG site, haifar da samuwar guanidinohydantoin moiety a matsayin babban samfurin.Ba a samu shaidar kafa wuraren da ba a san su ba.Waɗannan sakamakon sun nuna cewa nau'in oxidized na 8-oxoG, mai yiwuwa guanidinohydantoin, na iya yin kuskuren karantawa da kuskuren dNTPs yayin haɗin DNA.Idan irin wannan tsari ya faru a cikin vivo, zai wakilci raunin mutagenic ma'ana wanda zai kai ga G->T da G-> C.Koyaya, daidaitaccen nau'in oxidized na 8-oxoA da farko yana nuna daidai shigar T yayin haɗin DNA tare da Kf exo-.