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PMID: 20067321 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Biochemistry ·Vol. 49 ·No. 6 ·2010-02-16 ·Pages 1053-5

Jaruga P, Xiao Y, Vartanian V, Lloyd RS, Dizdaroglu M

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 aimed at elucidating the mechanism of action of NEIL1 in NER are warranted.

MeSH Terms
Animals DNA Damage/genetics DNA Glycosylases/deficiency,genetics,physiology DNA Repair/genetics DNA Replication/genetics Deoxyadenosines/genetics,metabolism Guanine/analogs & derivatives,metabolism Liver/chemistry,metabolism Mice Mice, Knockout Pyrimidines/metabolism Stereoisomerism Substrate Specificity/genetics
Chemicals
Deoxyadenosines Pyrimidines 8,5'-cyclo-2'-deoxyadenosine 2,6-diamino-4-hydroxy-5-formamidopyrimidine 8-hydroxyguanine Guanine DNA Glycosylases Neil1 protein, mouse Ogg1 protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Jaruga Pawel
Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA.
Xiao Yan
Vartanian Vladimir
Lloyd R Stephen
Dizdaroglu Miral
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Article Info
Journal
Biochemistry
Abbr.
Biochemistry
ISSN
1520-4995
DOI
10.1021/bi902161f
Published
2010-02-16
Pages
1053-5
Language
English
Region
United States
NLM ID
0370623
PMCID
PMC2817919
Subset
IM
Grants
NIDDK NIH HHS · R01 DK075974 · United States
NIDDK NIH HHS · DK075974 · United States
External Links
PubMed source DOI: 10.1021/bi902161f PMC Full Text View journal details
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