Towards a comprehensive view of 8-oxo-7,8-dihydro-2'-deoxyguanosine: Highlighting the intertwined roles of DNA damage and epigenetics in genomic instability.
8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a major product of DNA oxidation, is a pre-mutagenic lesion which is prone to mispair, if left unrepaired, with 2'-deoxyadenosine during DNA replication. While unrepaired or incompletely repaired 8-oxodG has classically been associated with genome instability and cancer, it has recently been reported to have a role in the epigenetic regulation of gene expression. Despite the growing collection of genome-wide 8-oxodG mapping studies that have been used to provide new insight on the functional nature of 8-oxodG within the genome, a comprehensive view that brings together the epigenetic and the mutagenic nature of the 8-oxodG is still lacking. To help address this gap, this review aims to provide (i) a description of the state-of-the-art knowledge on both the mutagenic and epigenetic roles of 8-oxodG; (ii) putative molecular models through which the 8-oxodG can cause genome instability; (iii) a possible molecular model on how 8-oxodG, acting as an epigenetic signal, could cause the translocations and deletions which are associated with cancer.
['Gorini|Francesca|F|', 'Scala|Giovanni|G|', 'Cooke|Marcus S|MS|', 'Majello|Barbara|B|', 'Amente|Stefano|S|']
D000080242:8-Hydroxy-2'-Deoxyguanosine D000818:Animals D004247:DNA D004249:DNA Damage D004260:DNA Repair D044127:Epigenesis, Genetic D056890:Eukaryota D042822:Genomic Instability D006801:Humans D008957:Models, Genetic
Genome instability 8-oxodG Cancer Base excision repair Double-strand break Single-Strand break TOP1-DPC