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DNA Res. 2014 Dec;21(6):603-12. doi: 10.1093/dnares/dsu023. Epub 2014 Jul 9.

Genome-wide profiling of 8-oxoguanine reveals its association with spatial positioning in nucleus.

Author information

1
Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
2
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan.
3
Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan Japan Science and Technology Agency, CREST, Fukuoka 812-8582, Japan mikita@bioreg.kyushu-u.ac.jp toyokuni@med.nagoya-u.ac.jp.
4
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan mikita@bioreg.kyushu-u.ac.jp toyokuni@med.nagoya-u.ac.jp.

Abstract

8-Oxoguanine (8-oxoG) is one of the most common DNA lesions generated by reactive oxygen species. In this study, we analysed the genome-wide distribution profile of 8-oxoG by combining immunoprecipitation by antibodies specific for the DNA fragments containing 8-oxoG with a microarray that covers rat genome. Genome-wide mapping of 8-oxoG in normal rat kidney revealed that 8-oxoG is preferentially located at gene deserts. We did not observe differences in 8-oxoG levels between groups of genes with high and low expression, possibly because of the generally low 8-oxoG levels in genic regions compared with gene deserts. The distribution of 8-oxoG and lamina-associated domains (LADs) were strongly correlated, suggesting that the spatial location of genomic DNA in the nucleus determines the susceptibility to oxidative modifications. One possible explanation for high 8-oxoG levels in LADs is that the nuclear periphery is more susceptible to the oxidative damage caused by the extra-nuclear factors. Moreover, LADs have a rather compact conformation, which may limit the recruitment of repair components to the modified bases.

KEYWORDS:

8-oxoguanine; DNA modification; lamina-associated domain; oxidative stress

PMID:
25008760
PMCID:
PMC4263294
DOI:
10.1093/dnares/dsu023
[Indexed for MEDLINE]
Free PMC Article

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