MoCoLo: a testing framework for motif co-localization.

Sequence-level data offers insights into biological processes through the interaction of two or more genomic features from the same or different molecular data types. Within motifs, this interaction is often explored via the co-occurrence of feature genomic tracks using fixed-segments or analytical tests that respectively require window size determination and risk of false positives from over-simplified models. Moreover, methods for robustly examining the co-localization of genomic features, and thereby understanding their spatial interaction, have been elusive.

A 'light-up' intercalator displacement assay for detection of triplex DNA stabilizers.

Here, we developed a coralyne-based, 'light-up' intercalator displacement assay to identify molecular stabilizers of triplex DNA using a sequence from a chromosomal breakpoint hotspot in the human c-MYC oncogene. Its potential to identify triplex DNA ligands was demonstrated using BePI and doxorubicin. Identification of triplex-interacting ligands may allow the regulation of genetic instability in human genomes.

Modulation of DNA structure formation using small molecules.

Genome integrity is essential for proper cell function such that genetic instability can result in cellular dysfunction and disease. Mutations in the human genome are not random, and occur more frequently at "hotspot" regions that often co-localize with sequences that have the capacity to adopt alternative (i.e.

A tunable assay for modulators of genome-destabilizing DNA structures.

Regions of genomic instability are not random and often co-localize with DNA sequences that can adopt alternative DNA structures (i.e. non-B DNA, such as H-DNA).

Alternative DNA structure formation in the mutagenic human c-MYC promoter.

Mutation 'hotspot' regions in the genome are susceptible to genetic instability, implicating them in diseases. These hotspots are not random and often co-localize with DNA sequences potentially capable of adopting alternative DNA structures (non-B DNA, e.g.

Structural basis for bifunctional zinc(II) macrocyclic complex recognition of thymine bulges in DNA.

The zinc(II) complex of 1-(4-quinoylyl)methyl-1,4,7,10-tetraazacyclododecane (cy4q) binds selectively to thymine bulges in DNA and to a uracil bulge in RNA. Binding constants are in the low-micromolar range for thymine bulges in the stems of hairpins, for a thymine bulge in a DNA duplex, and for a uracil bulge in an RNA hairpin. Binding studies of Zn(cy4q) to a series of hairpins containing thymine bulges with different flanking bases showed that the complex had a moderate selectivity for thymine bulges with neighboring purines.

Recognition of thymine in DNA bulges by a Zn(II) macrocyclic complex.

A Zn(II) macrocyclic complex with appended quinoline is a bifunctional recognition agent that uses both the Zn(II) center and the pendent aromatic group to bind to thymine in bulges with good selectivity over DNA containing G, C or A bulges. Spectroscopic studies show that the stem containing the bulge stays largely intact in a DNA hairpin with the Zn(II) complex bound to the thymine bulge.

Synthesis and luminescence properties of a trinucleotide-europium(III) complex conjugate.

Two trinucleotide conjugates of the macrocyclic ligand 1,4,7-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane are prepared. One contains only DNA (1) and the second is a chimeric RNA/DNA conjugate (2). The synthetic methodology used to prepare the trinucleotide macrocyclic ligand conjugates is based on the introduction of a convertible nucleoside which has an electrophilic function to facilitate the attachment of any nucleophilic ligand to the 5-position of the 3-nucleoside unit.

Cleavage of a RNA analog containing uridine by a bifunctional dinuclear Zn(II) catalyst.

The macrocyclic ligand, 1,4-bis((1-oxa-4,7,10-triazacyclododecan-7-yl)methyl)benzene (L1) is prepared. L1 binds two Zn(II) ions at neutral pH to form Zn(2)(L1) as studied by using pH-potentiometric titrations. Zn(2)(L1) binds two uridines at pH 7.