Most cited article - PubMed ID 22856523
Superhelical DNA as a preferential binding target of 14-3-3γ protein
Cruciforms occur when inverted repeat sequences in double-stranded DNA adopt intra-strand hairpins on opposing strands. Biophysical and molecular studies of these structures confirm their characterization as four-way junctions and have demonstrated that several factors influence their stability, including overall chromatin structure and DNA supercoiling. Here, we review our understanding of processes that influence the formation and stability of cruciforms in genomes, covering the range of sequences shown to have biological significance. It is challenging to accurately sequence repetitive DNA sequences, but recent advances in sequencing methods have deepened understanding about the amounts of inverted repeats in genomes from all forms of life. We highlight that, in the majority of genomes, inverted repeats are present in higher numbers than is expected from a random occurrence. It is, therefore, becoming clear that inverted repeats play important roles in regulating many aspects of DNA metabolism, including replication, gene expression, and recombination. Cruciforms are targets for many architectural and regulatory proteins, including topoisomerases, p53, Rif1, and others. Notably, some of these proteins can induce the formation of cruciform structures when they bind to DNA. Inverted repeat sequences also influence the evolution of genomes, and growing evidence highlights their significance in several human diseases, suggesting that the inverted repeat sequences and/or DNA cruciforms could be useful therapeutic targets in some cases.
- Keywords
- DNA base sequence, DNA structure, DNA supercoiling, cruciform, epigenetics, genome stability, inverted repeat, replication, transcription,
- MeSH
- DNA genetics MeSH
- Nucleic Acid Conformation MeSH
- DNA, Cruciform MeSH
- Humans MeSH
- Nucleic Acids * MeSH
- Inverted Repeat Sequences MeSH
- Repetitive Sequences, Nucleic Acid genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- DNA MeSH
- DNA, Cruciform MeSH
- Nucleic Acids * MeSH
MOTIVATION: The NCBI database contains mitochondrial DNA (mtDNA) genomes from numerous species. We investigated the presence and locations of inverted repeat sequences (IRs) in these mtDNA sequences, which are known to be important for regulating nuclear genomes. RESULTS: IRs were identified in mtDNA in all species. IR lengths and frequencies correlate with evolutionary age and the greatest variability was detected in subgroups of plants and fungi and the lowest variability in mammals. IR presence is non-random and evolutionary favoured. The frequency of IRs generally decreased with IR length, but not for IRs 24 or 30 bp long, which are 1.5 times more abundant. IRs are enriched in sequences from the replication origin, followed by D-loop, stem-loop and miscellaneous sequences, pointing to the importance of IRs in regulatory regions of mitochondrial DNA. AVAILABILITY AND IMPLEMENTATION: Data were produced using Palindrome analyser, freely available on the web at http://bioinformatics.ibp.cz. CONTACT: vaclav@ibp.cz. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
