Circular Structures in Retroviral and Cellular Genomes

Abstract

A computer program for predicting DNA bending from nucleotide sequence was used to identify circular structures in retroviral and cellular genomes. An 830-base pair circular structure was located in a control region near the center of the genome of the human immunodeficiency virus type I (HIV-I). This unusual structure displayed relatively smooth planar bending throughout its length. The structure is conserved in diverse isolates of HIV-I, HIV-II, and simian immunodeficiency viruses, which implies that it is under selective constraints. A search of all sequences in the GenBank data base was carried out in order to identify similar circular structures in cellular DNA. The results revealed that the structures are associated with a wide range of sequences that undergo recombination, including most known examples of DNA inversion and subtelomeric translocation systems. Circular structures were also associated with replication and transposition systems where DNA looping has been implicated in the generation of large protein-DNA complexes. Experimental evidence for the structures was provided by studies which demonstrated that two sequences detected as circular by computer preferentially formed covalently closed circles during ligation reactions in vitro when compared to nonbent fragments, bent fragments with noncircular shapes, and total genomic DNA. In addition, a single T 3 C substitution in one of these sequences rendered it less planar as seen by computer analysis and significantly reduced its rate of ligase-catalyzed cyclization. These results permit us to speculate that intrinsically circular structures facilitate DNA looping during formation of the large protein-DNA complexes that are involved in site-and region-specific recombination and in other genomic processes.Sequence-directed bending of DNA is one factor that causes local variations in the structure of genomes (reviewed by

Selective Nucleosome Disruption by Drugs That Bind in the Minor Groove of DNA

“…2 This linear segment preferentially forms a circle in ligation reactions and displays marked electrophoretic retardation that is comparable to that seen with kintoplast DNA (33). As seen in the bottom of Fig.…”

“…Plasmid DR36 containing a segment of the RNA polymerase II gene (32) from Caenorhabditis elegans (AS# M2923S) was kindly provided by Dr. David Bird (University of California, Riverside, CA). Subclones from this plasmid containing the circular intron D and nonbent exon segments were inserted into the EcoRI site of pUC18 as described previously (33). The dove satellite sequence has also been described (34) while the 5 S rRNA gene from sea urchin (35) was obtained from Dr. Robert Simpson and subcloned into the EcoRI site of pUC18.…”

“…9 show that selective nucleosome loss induced by DAPI does occur under physiologically relevant conditions which illustrates that these drugs do have the in vivo potential to exert their effects both during and after nucleosome assembly. Circular DNA structures that arise from the A-tract bending phenomenon are rare in the genome and are frequently found in regulatory regions for replication, recombination, and transcription (33). It will be of interest to determine if the drugs can be used to target selectively nucleosome disruption in these regions in viable cells.…”

“…Assembly-The studies described below focus on a DNA segment from an intron of the C. elegans RNA polymerase II gene (33,40). 2 This linear segment preferentially forms a circle in ligation reactions and displays marked electrophoretic retardation that is comparable to that seen with kintoplast DNA (33).…”

Tertiary Structures of the Escherichia coli and Human Chromosome 21 Molecules of DNA

“…These properties are typical of the bacterial nucleoid (14) including the E. coli DNA (15) as well as the eukaryotic chromosomes that are also composed of domains and loops (16 -18). Circles or loops were also predicted to occur in the HIV provirus DNA (19). Figure 2 was generated using the information extracted from the crystal structures of B-DNA.…”