CO protects cells from iron-Fenton oxidative DNA damage in and humans.

While hydroxyl radical is commonly named as the Fenton product responsible for DNA and RNA damage in cells, here we demonstrate that the cellular reaction generates carbonate radical anion due to physiological bicarbonate levels. In human and models, their transcriptomes were analyzed by RNA direct nanopore sequencing of ribosomal RNA and chromatography coupled to electrochemical detection to quantify oxidation products in order to follow the bicarbonate dependency in HO-induced oxidation. These transcriptomic studies identified physiologically relevant levels of bicarbonate focused oxidation on the guanine base favorably yielding 8-oxo-7,8-dihydroguanine (OG).

Why the ROS matters: One-electron oxidants focus DNA damage and repair on G-quadruplexes for gene regulation.

Hydrogen peroxide is a precursor to reactive oxygen species (ROS) in cells because of its high reactivity with iron(II) carbonate complexes formed in the labile iron pool due to a high concentration of intracellular bicarbonate (25-100 mM). This chemistry leads to the formation of carbonate radical anion rather than hydroxyl radical, and unlike the latter ROS, CO is a milder one-electron oxidant with high specificity for guanine oxidation in DNA and RNA. In addition to metabolism, another major source of DNA oxidation is inflammation which generates peroxynitrite, another precursor to CO via reaction with dissolved CO.

Apurinic/Apyrimidinic Endodeoxyribonuclease 1 modulates RNA G-quadruplex folding of miR-92b and controls its expression in cancer cells.

In the last decade, several novel functions of the mammalian Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1) have been discovered, going far beyond its canonical function as DNA repair enzyme and unveiling its potential roles in cancer development. Indeed, it was shown to be involved in DNA G-quadruplex biology and RNA metabolism, most importantly in the miRNA maturation pathway and the decay of oxidized or abasic miRNAs during oxidative stress conditions. In recent years, several noncanonical pathways of miRNA biogenesis have emerged, with a specific focus on guanosine-rich precursors that can form RNA G-quadruplex (rG4) structures.

CO protects cells from iron-Fenton oxidative DNA damage in E. coli and humans.

Whereas hydroxyl radical is commonly named as the Fenton product responsible for DNA and RNA damage in cells, here we demonstrate that the cellular reaction generates carbonate radical anion due to physiological levels of bicarbonate. Analysis of the metabolome, transcriptome and, in human cells, the nuclear genome shows a consistent buffering of HO-induced oxidative stress leading to one common pathway, namely guanine oxidation. Particularly revealing are nanopore-based studies of direct RNA sequencing of cytosolic and mitochondrial ribosomal RNA along with glycosylase-dependent qPCR studies of oxidative DNA damage in telomeres.

Parent attitudes towards predictive testing for autism in the first year of life.

Background: Emerging biomarker technologies (e.g., MRI, EEG, digital phenotyping, eye-tracking) have potential to move the identification of autism into the first year of life.