On the epigenetic role of guanosine oxidation

Abstract

Chemical modifications of DNA and RNA regulate genome functions or trigger mutagenesis resulting in aging or cancer. Oxidations of macromolecules, including DNA, are common reactions in biological systems and often part of regulatory circuits rather than accidental events.DNA alterations are particularly relevant since the unique role of nuclear and mitochondrial genome is coding enduring and inheritable information. Therefore, an alteration in DNA may represent a relevant problem given its transmission to daughter cells. At the same time, the regulation of gene expression allows cells to continuously adapt to the environmental changes that occur throughout the life of the organism to ultimately maintain cellular homeostasis.Here we review the multiple ways that lead to DNA oxidation and the regulation of mechanisms activated by cells to repair this damage. Moreover, we present the recent evidence suggesting that DNA damage caused by physiological metabolism acts as epigenetic signal for regulation of gene expression. In particular, the predisposition of guanine to oxidation might reflect an adaptation to improve the genome plasticity to redox changes.

Role of Poly [ADP-ribose] Polymerase 1 in Activating the Kirsten ras (KRAS) Gene in Response to Oxidative Stress

“…This is indeed in keeping with pull-down and Western blot assays showing that the G4 motifs of the KRAS promoter form together with PARP-1, MAZ and hnRNP A1 the transcription pre-initiation complex. It is possible that 8OG behaves as an epigenetic mark for the recruitment to the promoter of the transcription factors [ 51 , 52 , 53 ]. We observed that PARP-1 binds to both G4 32R and G4 mid, either in a wild-type or oxidized form.…”

Cheating on forensic hair testing? Detection of potential biomarkers for cosmetically altered hair samples using untargeted hair metabolomics

“…Oxidation of guanosine to 8-oxo-7,8-dihydroguanosine (8-oxo-dG) is the most frequent oxidation product in DNA. 46 Compared to adenosine, guanosine might therefore likewise be more prone to bleaching processes. Biomarker ratios of decreasing guanosine and increasing adenosine were formed, but did not result in improved discrimination.…”

Analytical and Structural Studies for the Investigation of Oxidative Stress in Guanine Oligonucleotides

“…It was also found that the levels of o 8 dGuo noticeably increased with the increase of the Air Quality Index, and the method is a viable tool to investigate the relationship between o 8 dGuo levels and the effect of air pollution. o 8 dGuo removal is tightly regulated by external and internal stimuli, e.g., ROS accumulation that is affected by air pollution as well ( Figure 12) [7].…”

“…OG may alter gene expression and its transcriptional impact is dependent on the coding versus template strand of OG occurrence, and it can temporarily stop or even completely abolish mRNA synthesis. The role of guanine lesions is the complex process of epigenetic regulation that has been reviewed recently by several authors [1,5,[7][8][9][10][11][12][13][14][15][16][17]. Pertinent to this multifaceted role is the analytical detection, quantification and structural studies of the facilitated formation of OG in G-rich oligonucleotide sequences, in particular, G-quadruplexes and their hydrolysis products (nucleosides, nucleobases), which is the subject of the present review.…”

“…OG is a target for base excision repair initiated by the enzyme OG-glycosylase 1 (OGG1). Traditionally, the formation of OG is considered as a biomarker of a mutagenetic event [4] but it could be epigenetic by functioning as a transcriptional regulator [5,6] or, in general, as a tool to improve the genome plasticity to redox changes [7]. The formation of OG is either beneficial or detrimental depending on the gene product that is formed from the OG-containing promoter [5].…”