期刊
NUCLEIC ACIDS RESEARCH
卷 47, 期 1, 页码 221-236出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky1152
关键词
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资金
- AIRC [IG13173, IG 17: IG-2017-20162]
- EC-FP7-ERC-InMec [341131]
- Epigenomics Flagship Project-EPIGEN, C.N.R.
- Grant MOVIE of the Rete delle Biotecnologie, Campania
- CINECA ISCRA [IsC39_MSDDiM, IsC48_TraSMODa]
- ELIXIR ITA [ELIX_prj10]
8-Oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) is one of the major DNA modifications and a potent pre-mutagenic lesion prone to mispair with 2-deoxyadenosine (dA). Several thousand residues of 8-oxodG are constitutively generated in the genome of mammalian cells, but their genomic distribution has not yet been fully characterized. Here, by using OxiDIP-Seq, a highly sensitive methodology that uses immuno-precipitation with efficient anti-8-oxodG antibodies combined with high-throughput sequencing, we report the genome-wide distribution of 8-oxodG in human non-tumorigenic epithelial breast cells (MCF10A), and mouse embryonic fibroblasts (MEFs). OxiDIP-Seq revealed sites of 8-oxodG accumulation overlapping with H2AX ChIP-Seq signals within the gene body of transcribed long genes, particularly at the DNA replication origins contained therein. We propose that the presence of persistent single-stranded DNA, as a consequence of transcription-replication clashes at these sites, determines local vulnerability to DNA oxidation and/or its slow repair. This oxidatively-generated damage, likely in combination with other kinds of lesion, might contribute to the formation of DNA double strand breaks and activation of DNA damage response.
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