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

[Image: see text] 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-formamidop...

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Autores principales: Jaruga, Pawel, Xiao, Yan, Vartanian, Vladimir, Lloyd, R. Stephen, Dizdaroglu, Miral
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2010
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817919/
https://www.ncbi.nlm.nih.gov/pubmed/20067321
http://dx.doi.org/10.1021/bi902161f
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author Jaruga, Pawel
Xiao, Yan
Vartanian, Vladimir
Lloyd, R. Stephen
Dizdaroglu, Miral
author_facet Jaruga, Pawel
Xiao, Yan
Vartanian, Vladimir
Lloyd, R. Stephen
Dizdaroglu, Miral
author_sort Jaruga, Pawel
collection PubMed
description [Image: see text] 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.
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spelling pubmed-28179192010-02-09 Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines Jaruga, Pawel Xiao, Yan Vartanian, Vladimir Lloyd, R. Stephen Dizdaroglu, Miral Biochemistry [Image: see text] 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. American Chemical Society 2010-01-12 2010-02-16 /pmc/articles/PMC2817919/ /pubmed/20067321 http://dx.doi.org/10.1021/bi902161f Text en Copyright © 2010 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Jaruga, Pawel
Xiao, Yan
Vartanian, Vladimir
Lloyd, R. Stephen
Dizdaroglu, Miral
Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines
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
title_full Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines
title_fullStr Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines
title_full_unstemmed Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines
title_short Evidence for the Involvement of DNA Repair Enzyme NEIL1 in Nucleotide Excision Repair of (5′R)- and (5′S)-8,5′-Cyclo-2′-deoxyadenosines
title_sort evidence for the involvement of dna repair enzyme neil1 in nucleotide excision repair of (5′r)- and (5′s)-8,5′-cyclo-2′-deoxyadenosines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817919/
https://www.ncbi.nlm.nih.gov/pubmed/20067321
http://dx.doi.org/10.1021/bi902161f
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