Inverted repeats, stem‐loops, and cruciforms: Significance for initiation of DNA replication

Abstract

Inverted repeats occur nonrandomly in the DNA of most organisms. Stem-loops and cruciforms can form from inverted repeats. Such structures have been detected in pro- and eukaryotes. They may affect the supercoiling degree of the DNA, the positioning of nucleosomes, the formation of other secondary structures of DNA, or directly interact with proteins. Inverted repeats, stem-loops, and cruciforms are present at the replication origins of phage, plasmids, mitochondria, eukaryotic viruses, and mammalian cells. Experiments with anti-cruciform antibodies suggest that formation and stabilization of cruciforms at particular mammalian origins may be associated with initiation of DNA replication. Many proteins have been shown to interact with cruciforms, recognizing features like DNA crossovers, four-way junctions, and curved/bent DNA of specific angles. A human cruciform binding protein (CBP) displays a novel type of interaction with cruciforms and may be linked to initiation of DNA replication.

Enhancement of p53 sequence-specific binding by DNA supercoiling

“…Considering the local level of DNA supercoiling in eucaryotic DNA as an extremely dynamic system (van Holde and Zlatanova, 1994;Pearson et al, 1996) and the relations between the p53 and DNA topoisomerases as well as the results of this and earlier papers on p53 binding to scDNA (Palecek et al, 1997(Palecek et al, , 2001Kim et al, 1999;Mazur et al, 1999;Brazda et al, 2000;Brazdova et al, 2002;Jagelska et al, 2002), we propose new aspects of the regulation of p53 SSDB. We predict that, in the complex p53-regulatory network, p53 DNA binding is determined not only by properties of p53 (potentially resulting from postsynthetic modification and protein-protein interactions), but also by various properties of DNA, including local DNA superhelix density and the abilities of the given p53 target and its flanking sequences to undergo conformational changes.…”

“…In contrast to the prokaryotic genome, the eucaryotic genome was long believed to not be under superhelical stress due to accommodation of DNA writhing around histone octamers in nucleosomes (van Holde and Zlatanova, 1994;Pearson et al, 1996). The actively transcribing portion of the eucaryotic genome was, however, shown to contain unconstrained supercoiling, part of which can be attributed to the process of transcription per se (van Holde and Zlatanova, 1994;Pearson et al, 1996). Using prokaryotic cells, it has been recently shown (Krasilnikov et al, 1999) that the effects of transcriptionally driven supercoiling are remarkably large scale in vivo (in the kbp range).…”

“…To explain this finding, some factors were proposed, including the action of an as-yet-unidentified p53 specific repressor (Gottifredi et al, 2001), but the involvement of DNA structure at or near the p53 target has not been discussed. It has been appreciated that supercoiling may up-and downregulate some promoters, while other promoters may remain uninfluenced (reviewed in Palecek, 1991;Yagil, 1991;Pearson et al, 1996). Considering the recent finding that superhelical stress is distributed throughout the entire replicating DNA molecule (both in vitro and in vivo) during the DNA replication (Peter et al, 1998), as well as the supercoil-induced suppression (Kim et al, 1999) or enhancement of p53 SSDB (Figure 2), we speculate that it is the change in DNA supercoiling and concomitant changes in local DNA structures that can affect DNA transcriptional activity when DNA replication is blocked.…”

“…DNA topology is of fundamental importance for a wide range of biological processes including DNA transcription, replication, recombination, control of gene expression, genome organization, etc (Palecek, 1991;Bates and Maxwell, 1993;Pearson et al, 1996). DNA protein binding is often supercoiling dependent.…”

Structure and Expression of the Gene Encoding Secretor‐Type Galactoside 2‐α‐l‐fucosyltransferase (FUT2)

“…lA), suggesting that some of the 3'-RACE products are artificial. While we do not know whether or not the genomic DNA of the FUT2 mRNA forms a stedloop structure, crucifordstedloop DNA structures have been shown to be functionally important for the initiation of DNA replication in prokaryotes and eukaryotes [26]. An endoribonuclease activity that degrades the mRNA of insulin-like growth factor I1 in crude cell extracts has been detected [27], and cleavage has occurred within a large stem-and-loop structure (approximately 2 kilobases) in the 3' untranslated region of this mRNA, which is a known mRNA-half-life determinant in intact cells 128, 291.…”