BIOMAT Database Logo BIOMAT Database Logo

Evidence for the involvement of DNA repair enzyme NEIL1 in nucleotide excision repair of (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines. 2010

Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Chemical Science and Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA.

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D003839 Deoxyadenosines Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule. Adenine Deoxyribonucleosides,Adenylyldeoxyribonucleosides,Deoxyadenosine Derivatives,Deoxyribonucleosides, Adenine,Derivatives, Deoxyadenosine
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004261 DNA Replication The process by which a DNA molecule is duplicated. Autonomous Replication,Replication, Autonomous,Autonomous Replications,DNA Replications,Replication, DNA,Replications, Autonomous,Replications, DNA
D006147 Guanine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities

Related Publications

Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
DNA damage products (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines as potential biomarkers in human urine for atherosclerosis.
March 2012, Biochemistry,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Repair efficiency of (5'S)-8,5'-cyclo-2'-deoxyguanosine and (5'S)-8,5'-cyclo-2'-deoxyadenosine depends on the complementary base.
November 2012, DNA repair,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Identification and quantification of (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines in human urine as putative biomarkers of oxidatively induced damage to DNA.
June 2010, Biochemical and biophysical research communications,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Incorporation of 5',8-cyclo-2'deoxyadenosines by DNA repair polymerases via base excision repair.
January 2022, DNA repair,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Structure of (5'S)-8,5'-cyclo-2'-deoxyguanosine in DNA.
December 2011, Journal of the American Chemical Society,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
The oxidative DNA lesion 8,5'-(S)-cyclo-2'-deoxyadenosine is repaired by the nucleotide excision repair pathway and blocks gene expression in mammalian cells.
July 2000, The Journal of biological chemistry,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Elevated urinary levels of 8-oxo-2'-deoxyguanosine, (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines, and 8-iso-prostaglandin F2α as potential biomarkers of oxidative stress in patients with prediabetes.
December 2016, DNA repair,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Kinetic and structural mechanisms of (5'S)-8,5'-cyclo-2'-deoxyguanosine-induced dna replication stalling.
January 2015, Biochemistry,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Stability of N-glycosidic bond of (5'S)-8,5'-cyclo-2'-deoxyguanosine.
November 2012, Chemical research in toxicology,
Pawel Jaruga, and Yan Xiao, and Vladimir Vartanian, and R Stephen Lloyd, and Miral Dizdaroglu
Synthesis of [1,3, NH2-(15)N3] (5'S)-8,5'-cyclo-2'-deoxyguanosine.
June 2013, Journal of labelled compounds & radiopharmaceuticals,
Copied contents to your clipboard!