Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines

• DOI: 10.1021/bi902161f
• Publication Date: 2010-01-13T02:16:01Z
• Authors: Pawel Jaruga; Yan Xiao; Vladimir Vartanian; R. Stephen Lloyd; Miral Dizdaroglu
• Keywords: DNA Replication; Mice, Knockout; 0301 basic medicine; Guanine; DNA Repair; Deoxyadenosines; Stereoisomerism; DNA Glycosylases; Substrate Specificity; 3. Good health; Mice; 03 medical and health sciences; Pyrimidines; Liver; Animals; DNA Damage

The DNA repair enzyme NEIL1 is a glycosylase that involved in the first step of base excision (BER) oxidatively induced damage. exhibits strong preference for 4,6-diamino-5-formamidopyrimidine (FapyAde) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) from with no specificity 8-hydroxyguanine (8-OH-Gua). In this study, we report on significant accumulation (5'R)-8,5'-cyclo-2'-deoxyadenosine (R-cdA) (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA) liver neil1(-/-) mice were not exposed to exogenous oxidative stress, while these lesions was observed control or ogg1(-/-) mice. Significant FapyGua detected both mice, 8-OH-Gua accumulated only. Since R-cdA S-cdA contain an 8,5'-covalent bond between sugar moieties, they cannot be repaired by BER. There evidence are nucleotide (NER). strongly points failure their repair, data suggest NER S-cdA. Further studies aimed at elucidating mechanism action warranted.