Production, Isolation, and Characterization of Stable Isotope-Labeled Standards for Mass Spectrometric Measurements of Oxidatively-Damaged Nucleosides in RNA.

RNA undergoes oxidatively induced damage in living organisms analogous to DNA. RNA is even more vulnerable to damage than DNA due to its greater abundance, single-strandedness, lack of repair and chromatin proteins shield, and instability, among other effects. RNA damage can adversely affect gene expression, leading to protein synthesis alterations, cell death, and other detrimental biological consequences.

Functional characterization of single nucleotide polymorphic variants of DNA repair enzyme NEIL1 in South Asian populations.

The base excision repair (BER) pathway is a precise and versatile mechanism of DNA repair that is initiated by DNA glycosylases. Endonuclease VIII-like 1 (NEIL1) is a bifunctional glycosylase/abasic site (AP) lyase that excises a damaged base and subsequently cleaves the phosphodiester backbone. NEIL1 is able to recognize and hydrolyze a broad range of oxidatively-induced base lesions and substituted ring-fragmented guanines, including aflatoxin-induced 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B (AFB-FapyGua).

Functional analyses of single nucleotide polymorphic variants of the DNA glycosylase NEIL1 in sub-Saharan African populations.

Nei-like glycosylase 1 (NEIL1) is a DNA repair enzyme that initiates the base excision repair (BER) pathway to cleanse the human genome of damage. The substrate specificity of NEIL1 includes several common base modifications formed under oxidative stress conditions, as well as the imidazole ring open adducts that are induced by alkylating agents following initial modification at N7 guanine. An example of the latter is the persistent and mutagenic 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B (AFB-FapyGua) adduct, resulting from the alkylating agent aflatoxin B (AFB) exo-8-9-epoxide.

Synthesis and Characterization of N-Labeled Aflatoxin B-Formamidopyrimidines and Aflatoxin B-N7-Guanine from a Partial Double-Stranded Oligodeoxynucleotide as Internal Standards for Mass Spectrometric Measurements.

Aflatoxin B (AFB) exposure through contaminated food is a primary contributor to hepatocellular carcinogenesis worldwide. Hepatitis B viral infections in livers dramatically increase the carcinogenic potency of AFB exposures. Liver cytochrome P450 oxidizes AFB to the epoxide, which in turn reacts with N7-guanine in DNA, producing the cationic -8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B adduct (AFB-N7-Gua).