Six nitroxide spin-labeled psoralen derivative have been synthesized and evaluated as probes for structural and dynamic studies. Sequence specific photoaddition of these derivatives to DNA oligonucleotides resulted in site-specifically cross-linked and spin-labeled oligomers. Comparison of the general line shape features of the observed electron paramagnetic resonance (EPR) spectra of several d...

Synthetic oligodeoxynucleotides represent promising tools for gene inhibition in live systems. Triple helix-forming oligonucleotides, which bind to double-stranded DNA, are of special interest since they are targeted to the gene itself rather than to its mRNA product, as in the antisense strategy. Triple helix-forming oligonucleotides can be coupled to DNA-modifying agents and used to introduce...

We report an action spectrum for the photoreversal of a psoralen cross-link joining two self-complementary DNA oligonucleotides. The cross-link was formed between two thymines (T) on opposite strands of the DNA oligomers and 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT). For comparison, we also present an action spectrum for the photoreversal of the isolated diadduct T-HMT-T. The wavelength...

cdx4, a caudal-related homeodomain-containing transcription factor, functions as a regulator of hox genes, thereby playing a critical role in anterior-posterior (A-P) patterning during embryogenesis. In zebrafish, homozygous deletion of the cdx4 gene results in a mutant phenotype known as kugelig, with aberrant A-P patterning and severe anemia characterized by decreased gata1 expression in the ...

The secondary structure of the SP6/mouse insulin precursor RNA was determined by psoralen cross-linking experiments. A series of long-range contacts occur within the left half of the pre-mRNA that contains the intervening sequence. Multiple secondary structures for the pre-mRNA exist since some of the interactions share common sites. In splicing buffer but without the splicing extract added, ma...

Oligonucleotides can bind as third strands of DNA in a sequence-specific manner in the major groove in homopurine/homopyrimidine stretches in duplex DNA. Here we use a 10-base triplex-forming oligonucleotide linked to a psoralen derivative at its 5' end to achieve site-specific, targeted mutagenesis in an intact, double-stranded lambda phage genome. Site-specific triplex formation delivers the ...

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously publi...

1,2-Dioxetanes, efficient chemical sources of triplet excited carbonyl compounds, were observed to be genotoxic in isolated DNA, bacteria, and cultured mammalian cells. In superhelical DNA of bacteriophage PM2, various alkyl- and hydroxyalkyl-substituted dioxetanes (1) induced predominantly endonuclease-sensitive base modifications and only few single strand breaks. With a specific endonuclease...

When chromatin is photoreacted with psoralen, crosslinks occur preferentially in the linker DNA between nucleosomes. The pattern of these crosslinks can be analysed by exonuclease digestion of random DNA fragments, since the exonucleases tested stop at sites of psoralen-crosslinks. Further digestion of these fragments with Sl-nuclease leads to DNA fragments of nucleosomal and polynucleosomal si...