2016
DOI: 10.1021/acs.jproteome.6b00717
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Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

Abstract: Long wavelength ultraviolet radiation (UVA, 320–400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG… Show more

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Cited by 11 publications
(11 citation statements)
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“…6-TG is an immunosuppressive agent that is incorporated in DNA, thus increasing skin sensitivity to UVA light through 1 O 2 generation. Photochemical activation of DNA-incorporated 6-TG has been shown to trigger DNA and protein oxidation. , However, there is a need to gain further information on the efficiency for UVA-excited 6-TG to generate 8-oxodGuo in cellular DNA and possibly secondary oxidation products such as dSp.…”
Section: Discussionmentioning
confidence: 99%
See 2 more Smart Citations
“…6-TG is an immunosuppressive agent that is incorporated in DNA, thus increasing skin sensitivity to UVA light through 1 O 2 generation. Photochemical activation of DNA-incorporated 6-TG has been shown to trigger DNA and protein oxidation. , However, there is a need to gain further information on the efficiency for UVA-excited 6-TG to generate 8-oxodGuo in cellular DNA and possibly secondary oxidation products such as dSp.…”
Section: Discussionmentioning
confidence: 99%
“…Photochemical activation of DNAincorporated 6-TG has been shown to trigger DNA and protein oxidation. 500,509 However, there is a need to gain further information on the efficiency for UVA-excited 6-TG to generate 8-oxodGuo in cellular DNA and possibly secondary oxidation products such as dSp.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…DNA 6-TG serves as both a target for crosslink formation and as a source of ROS. Confirmation that ROS also induce crosslinking between proteins and canonical DNA nucleobases was obtained from a comparative proteomic analysis of DPCs formed in cultured human cells treated with 6-TG or (the non DNA-integrated) ciprofloxacin in combination with UVA [83]. Stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry identified more than 2000 DNA-crosslinked proteins most of which are involved in gene expression or DNA repair/replication.…”
Section: Dna-protein Crosslinksmentioning
confidence: 97%
“…Thio group-bearing (deoxy)ribonucleotides have been extensively used as intrinsic photolabels to analyse the three-dimensional structure of RNA molecules, to identify contacts between nucleic acids and proteins, to detect epitranscriptomic marks, and to manipulate individual DNA molecules [ 40 , 41 , 42 , 43 , 44 ]. Similarly to halogenated nucleotides, thio-nucleotides such as 4-thio-2’-deoxyuridine (4-thiodU), 4-thio-5-bromo-2’-deoxyuridine (4-thio-5-Br-dU), 6-thioguanosine (6-thioG) or 4-thiothymidine (4-thioT) operate as UVA sensitizers while the latter is easily incorporated into DNA during replication [ 45 , 46 , 47 ].…”
Section: Introductionmentioning
confidence: 99%