Ibicuruzwa

Kwangirika kwa Oxidative kwishingira ADN mubisanzwe bituma habaho purine ya okiside, cyane cyane 7,8-dihydro-8-oxoguanine (8-oxoG) na 7,8-dihydro-8-oxoadenine (8-oxoA), iyambere ikaba nziza- bizwi na mutagenic lesion.Kubera ko 8-oxoG ishobora guhita ikomeza okiside ugereranije n’ibisanzwe bisanzwe, hashyizweho iperereza muri base mugihe cya synthesis ya ADN ihabanye nuburyo bwa okiside ya 8-oxoG muri vitro.Inyandikorugero ya sintetike irimo igikomere kimwe cya 8-oxoG yabanje kuvurwa hakoreshejwe okiside itandukanye ya electron imwe cyangwa mugihe cya ogisijeni ya ogisijeni imwe hanyuma ikorerwa primer yagabanijwe na parike ya Klenow exo- (Kf exo-), inyana thymus ADN polymerase alpha (pol alpha) ) cyangwa ADN yumuntu polymerase beta (pol beta).Bihuye na raporo zabanjirije iyi, dAMP na dCMP byinjijwemo guhitamo bitandukanye na 8-oxoG hamwe na polymerase zose uko ari eshatu.Igishimishije, okiside ya 8-oxoG yabonetse kugirango itere dAMP na dGMP yinjizamo ibisebe na Kf exo- hamwe no kubuza kwaguka kwaguka primer o guhurira ahabigenewe byahinduwe.Ikigeretse kuri ibyo, igikomere kigizwe nigihe cyo guhuza ADN na pol alpha na pol beta.Ubushakashatsi hamwe na 8-oxoA yahinduwe yicyitegererezo oligonucleotide yerekana ko byombi 8-oxoA nuburyo bwa okiside ya 8-oxoA yinjizamo dTMP na Kf exo-.Isesengura rusange rya sprometrike ya 8-oxoG irimo oligonucleotide mbere na nyuma ya okiside hamwe na IrCl62-bihuye na okiside yibibanza 8-oxoG, bigatuma habaho guanidinohydantoin moiety nkibicuruzwa byingenzi.Nta kimenyetso cyo gushinga ibibanza byabasike cyabonetse.Ibisubizo byerekana ko uburyo bwa okiside ya 8-oxoG, ishobora kuba guanidinohydantoin, ishobora kuyobora gusoma nabi no kwinjiza nabi DNTPs mugihe cya synthesis ya ADN.Niba inzira nkiyi yarabaye muri vivo, byerekana ingingo ya mutagenic lesion iganisha kuri G -> T na G -> C.Nyamara, uburyo bwa oxydeize ya 8-oxoA yerekana cyane cyane kwinjiza neza T mugihe cya ADN hamwe na Kf exo-.