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


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
07 05 2020
Historique:
accepted: 11 03 2020
revised: 09 03 2020
received: 05 12 2019
pubmed: 22 3 2020
medline: 28 7 2020
entrez: 22 3 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32198884
pii: 5810856
doi: 10.1093/nar/gkaa175
pmc: PMC7192600
doi:

Substances chimiques

8-Hydroxy-2'-Deoxyguanosine 88847-89-6
DNA 9007-49-2
PARP1 protein, human EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1 EC 2.4.2.30
DNA Glycosylases EC 3.2.2.-
oxoguanine glycosylase 1, human EC 3.2.2.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4309-4324

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Francesca Gorini (F)

Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.

Giovanni Scala (G)

Department of Biology, University of Naples 'Federico II', Naples, Italy.

Giacomo Di Palo (G)

Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.

Gaetano Ivan Dellino (GI)

Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Department of Oncology and Hemato-oncology, University of Milano, Milan, Italy.

Sergio Cocozza (S)

Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.

Pier Giuseppe Pelicci (PG)

Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Department of Oncology and Hemato-oncology, University of Milano, Milan, Italy.

Luigi Lania (L)

Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.

Barbara Majello (B)

Department of Biology, University of Naples 'Federico II', Naples, Italy.

Stefano Amente (S)

Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.

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