The generation of photoproducts of psoralen (POPs) might be relevant in cell death induced by psoralen plus UVA, namely PUVA, which is a recognized effective treatment for cutaneous T-cell lymphoma, chronic graft-versus-host disease, and psoriasis. We investigated the occurrence of POP-induced cell death and the underlying mechanisms. POPs were produced by irradiating a psoralen solution with U...

Torsional tension in DNA may be both a prerequisite for the efficient initiation of transcription and a consequence of the transcription process itself with the generation of positive torsional tension in front of the RNA polymerase and negative torsional tension behind it. To examine torsional tension in specific regions of genomic DNA in vivo, we developed an assay using photoactivated psoral...

PERSPECTIVES AND UMMARY .............................................................. 1152 INTRODUCTION ..................................................................................... 1155 ORGANIC AND STRUCTURAL CHEMISTRY OF PSORALEN AND ITS ADDUCTS ................................................................... 1158 Naturally Occurring Psoralens ........................................

Impaired DNA damage repair, especially deficient transcription-coupled nucleotide excision repair, leads to segmental progeroid syndromes in human patients as well as in rodent models. Furthermore, DNA double-strand break signalling has been pinpointed as a key inducer of cellular senescence. Several recent findings suggest that another DNA repair pathway, interstrand cross-link (ICL) repair, m...

Mitomycin C (MMC) induces various types of DNA damages that cause significant cytotoxicity to cells. Accordingly, repair of MMC-induced damages involves multiple repair pathways such as nucleotide excision repair, homologous recombination repair and translesion bypass repair pathways. Nonetheless, repair of the MMC-induced DNA damages in mammals have not been fully delineated. In this study, we...

Bulk DNA within the eukaryotic genome is torsionarily relaxed. However, unconstrained negative supercoils of DNA have been detected in few local domains of the genome through preferential binding of psoralen. To make a genome-wide survey for such domains, we introduced biotinylated psoralen into Drosophila salivary glands and visualized it on polytene chromosomes with fluorescent streptavidin. ...

PURPOSE To discuss the contribution of psoralen and bergapten metabolites on psoralens toxicity. METHODS Computational chemistry prediction of metabolic reactions and toxicophoric groups based on the expert systems Derek and Meteor. RESULTS a total of 15 metabolites were suggested for both psoralen and bergapten based on phase 1 and 2 biotransformations until the 3rd generation. Five toxico...

The removal of interstrand cross-links (ICLs) from DNA in higher eucaryotes is not well understood. Here, we show that processing of psoralen ICLs in mammalian cell extracts is dependent upon the mismatch repair complex hMutSbeta but is not dependent upon the hMutSalpha complex or hMlh1. The processing of psoralen ICLs is also dependent upon the nucleotide excision repair proteins Ercc1 and Xpf...

The repair of psoralen interstrand cross-links in the yeast Saccharomyces cerevisiae involves the DNA repair groups nucleotide excision repair (NER), homologous recombination (HR), and post-replication repair (PRR). In repair-proficient yeast cells cross-links induce double-strand breaks, in an NER-dependent process; the double-strand breaks are then repaired by HR. An alternate error-prone rep...

Potorous tridactylis (PTK2) cells growing in culture were treated with psoralen derivatives and dividing cells were located by phase-contrast microscopy. Psoralens, light-sensitive DNA-photoadducting drugs, were reacted with mitotic chromosomes through exposure to 365-nm light from an argon laser microbeam system. It was found that following mitosis and photoreaction, cells without nuclear enve...