Ru-TAP complexes and DNA: from photo-induced electron transfer to gene photo-silencing in living cells

• Published in: Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences physical, and engineering sciences, 2013-07, Vol.371 (1995), p.20120131-20120131
• Main Authors: Marcélis, Lionel, Moucheron, Cécile, Kirsch-De Mesmaeker, Andrée
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; DNA; DNA - drug effects; DNA - genetics; DNA - radiation effects; Electron Transfer; Electron Transport - drug effects; Electron Transport - radiation effects; Gene Silencing - drug effects; Gene Silencing - radiation effects; Human papillomavirus; Humans; Light; Neoplasms, Experimental - genetics; Neoplasms, Experimental - therapy; Oligonucleotides; Photo-Cross-Linking; Photochemistry; Photochemotherapy - methods; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - therapeutic use; Ruthenium Complexes
• ISSN: 1364-503X; 1471-2962
• DOI: 10.1098/rsta.2012.0131

In this review, examples of applications of the photo-induced electron transfer (PET) process between photo-oxidizing Ru-TAP (TAP = 1,4,5,8-tetraazaphenanthrene) complexes and DNA or oligodeoxynucleotides (ODNs) are discussed. Applications using a free Ru-TAP complex (not chemically anchored to an ODN) are first considered. In this case, the PET gives rise to the production of an irreversible adduct of the Ru complex on a guanine (G) base, with formation of a covalent bond. After absorption of a second photon, this adduct can generate a bi-adduct, whereby the same complex binds to a second G moiety. These bi-adduct formations are responsible for photo-cross-linking between two strands of a duplex, each containing a G base, or between two G moieties of a single strand such as a telomeric sequence, as demonstrated by polyacrylamide gel electrophoresis analyses or mass spectrometry. Scanning force microscopy also allows the detection of such photobridgings with plasmid DNA. Other applications, for example with Ru-ODN, i.e. ODN with chemically anchored Ru-TAP complexes, are also discussed. It is shown that such Ru-ODN probes containing a G base in their own sequences are capable of photo-cross-linking selectively with their targeted complementary sequences, and, in the absence of such targets, they self-photo-inhibit. Such processes are applied successfully in gene photo-silencing of human papillomavirus cancer cells.