As psoralen and other furocoumarin derivatives, intercalated between two base pairs of native DNA, under irradiation at 365 nm form inter-strand cross-linkings as a consequence of bifunctional addition, the writers have investigated the ability of psoralen to give such bifunctional photo­ additions, too, with nucleic acids with disordered or partilly disordered structure (denatured DNA and r-R ...

Triple helix-forming oligonucleotides covalently linked to psoralen can be specifically cross-linked to both strands of DNA at the triplex-duplex junction following UV irradiation. We have previously shown that a 15mer psoralen-oligonucleotide conjugate forming a triple helix on the promoter of the alpha subunit gene of the interleukin-2 receptor inhibits transcription of reporter plasmids tran...

We have examined the interaction of several psoralen derivatives with the RNA genome of Rous sarcoma virus (RSV). In the presence of long-wavelength uv light, 4,5’,8-trimethylpsoralen (trioxsalen) and its 4’-hydroxymethyl (HMT) and 4’-aminomethyl (AMT) derivatives all efficiently crosslinked the subunits of the RSV 70 S RNA complex into a nondissociable state. These psoralen derivatives also we...

To explore the ability of triplex-forming oligodeoxyribonucleotides (TFOs) to inhibit genes responsible for dominant genetic disorders, we used two TFOs to block expression of the human rhodopsin gene, which encodes a G protein-coupled receptor involved in the blinding disorder autosomal dominant retinitis pigmentosa. Psoralen-modified TFOs and UVA irradiation were used to form photoadducts at ...

Recent evidence suggests a role for base excision repair (BER) proteins in the response to DNA interstrand crosslinks, which block replication and transcription, and lead to cell death and genetic instability. Employing fluorescently tagged fusion proteins and laser microirradiation coupled with confocal microscopy, we observed that the endonuclease VIII-like DNA glycosylase, NEIL1, accumulates...

The biosynthesis of some furocoumarins present in Ruta graveolens has been studied administering labeled psoralen, xanthotoxin, rutaretin, marmesin and 7-hydroxycoumarin-derivatives. The results obtained indicate that the biosynthetic pathway involves not only psoralen, but also xanthotoxin and bergapten, by means of methoxylation or demethoxylation reactions. Moreover results achieved from adm...

Psoralens linked to triplex-forming oligonucleotides (psoTFOs) have been used in conjunction with laser-induced two-photon excitation (TPE) to damage a specific DNA target sequence. To demonstrate that TPE can initiate photochemistry resulting in psoralen-DNA photoadducts, target DNA sequences were incubated with psoTFOs to form triple-helical complexes and then irradiated in liquid solution wi...

UvrA, UvrB, and UvrC initiate nucleotide excision repair by incising a damaged DNA strand on each side of the damaged nucleotide. This incision reaction is substoichiometric with regard to UvrB and UvrC, suggesting that both proteins remain bound following incision and do not "turn over." The addition of only helicase II to such reaction mixtures turns over UvrC; UvrB turnover requires the addi...

DNA interstrand crosslinks (ICLs) represent a severe form of damage that blocks DNA metabolic processes and can lead to cell death or carcinogenesis. The repair of DNA ICLs in mammals is not well characterized. We have reported previously that a key protein complex of nucleotide excision repair (NER), XPA-RPA, recognizes DNA ICLs. We now report the use of triplex technology to direct a site-spe...

Psoralen ultraviolet A (PUVA) is a proven modality in dermatological therapeutics. It is widely practiced in the treatment of psoriasis, vitiligo, atopic eczema, certain skin cancers, photosensitivity dermatoses, alopecia areata, graft-versus-host disease and morphea.1-3 In presence of UVA, psoralen intercalates between the DNA base pairs forming functional adducts, free radicals and reactive o...