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Publication Citation: Evidence for the involvement of DNA repair enzyme NEIL1 in nucleotide excision repair of (5'R)- and (5'S)-8,5'-Cyclo-2'-deoxyadenosines

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Author(s): Pawel Jaruga; Yan Xiao; Vladimir Vartanian; R S. Lloyd; M Miral Dizdar;
Title: Evidence for the involvement of DNA repair enzyme NEIL1 in nucleotide excision repair of (5'R)- and (5'S)-8,5'-Cyclo-2'-deoxyadenosines
Published: February 16, 2010
Abstract: The DNA repair enzyme NEIL1 is a DNA glycosylase that is involved in the first step of base excision repair (BER) of oxidatively induced DNA damage. NEIL1 exhibits a strong preference for excision of 4,6-diamino-5-formamidopyrimidine (FapyAde) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) from DNA with no specificity for 8-hydroxyguanine (8-OH-Gua). In this study, we report on the significant accumulation of (5'R)-8,5'-cyclo-2'-deoxyadenosine (R-cdA) and (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA) in liver DNA of neil1 / mice that were not exposed to exogenous oxidative stress, while no accumulation of these lesions was observed in liver DNA from control or ogg1 / mice. Significant accumulation of FapyGua was detected in liver DNA of both neil1 / and ogg1 / mice, while 8-OH-Gua accumulated in ogg1 / only. Since R-cdA and S-cdA contain an 8,5'-covalent bond between the base and sugar moieties, they cannot be repaired by BER. There is evidence that these lesions are repaired by nucleotide excision repair (NER). Since the accumulation of R-cdA and S-cdA in neil1 / mice strongly points to the failure of their repair, these data suggest that NEIL1 is involved in NER of R-cdA and S-cdA. Further studies are warranted to elucidate the mechanism of action of NEIL1 in NER.
Citation: Biochemistry
Volume: 49
Issue: 6
Pages: pp. 1053 - 1055
Keywords: Base Excision Repair, DNA Glycosylases, NEIL1, Nucleotide excision repair, LC/MS/MS
Research Areas: Life Sciences Research, DNA