The genomic landscape of 8-oxodG reveals enrichment at specific inherently fragile promoters

Francesca Gorini, Giovanni Scala, Giacomo Di Palo, Gaetano Ivan Dellino, Sergio Cocozza, Pier Giuseppe Pelicci, Luigi Lania, Barbara Majello, Stefano Amente

Research output: Contribution to journalArticlepeer-review

Abstract

8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most common marker of oxidative stress and its accumulation within the genome has been associated with major human health issues such as cancer, aging, cardiovascular and neurodegenerative diseases. The characterization of the different genomic sites where 8-oxodG accumulates and the mechanisms underlying its formation are still poorly understood. Using OxiDIP-seq, we recently derived the genome-wide distribution of 8-oxodG in human non-tumorigenic epithelial breast cells (MCF10A). Here, we identify a subset of human promoters that accumulate 8-oxodG under steady-state condition. 8-oxodG nucleotides co-localize with double strand breaks (DSBs) at bidirectional and CG skewed promoters and their density correlate with RNA Polymerase II co-occupancy and transcription. Furthermore, by performing OxiDIP-seq in quiescent (G0) cells, we found a strong reduction of oxidatively-generated damage in the majority of 8-oxodG-positive promoters in the absence of DNA replication. Overall, our results suggest that the accumulation of 8-oxodG at gene promoters occurs through DNA replication-dependent or -independent mechanisms, with a possible contribution to the formation of cancer-associated translocation events.

Original languageEnglish
Pages (from-to)4309-4324
Number of pages16
JournalNucleic Acids Research
Volume48
Issue number8
DOIs
Publication statusPublished - May 7 2020

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'The genomic landscape of 8-oxodG reveals enrichment at specific inherently fragile promoters'. Together they form a unique fingerprint.

Cite this