Abstract
DNA is a fundamentally important molecule for all cellular organisms due to its biological role as the store of hereditary, genetic information. On the one hand, genomic DNA is very stable, both in chemical and biological contexts, and this assists its genetic functions. On the other hand, it is also a dynamic molecule, and constant changes in its structure and sequence drive many biological processes, including adaptation and evolution of organisms. DNA genomes contain significant amounts of repetitive sequences, which have divergent functions in the complex processes that involve DNA, including replication, recombination, repair, and transcription. Through their involvement in these processes, repetitive DNA sequences influence the genetic instability and evolution of DNA molecules and they are located non-randomly in all genomes. Mechanisms that influence such genetic instability have been studied in many organisms, including within human genomes where they are linked to various human diseases. Here, we review our understanding of short, simple DNA repeats across a diverse range of bacteria, comparing the prevalence of repetitive DNA sequences in different genomes. We describe the range of DNA structures that have been observed in such repeats, focusing on their propensity to form local, non-B-DNA structures. Finally, we discuss the biological significance of such unusual DNA structures and relate this to studies where the impacts of DNA metabolism on genetic stability are linked to human diseases. Overall, we show that simple DNA repeats in bacteria serve as excellent and tractable experimental models for biochemical studies of their cellular functions and influences.
Highlights
deoxyribonucleic acid (DNA) molecules are the store of genetic information for all cellular organisms
Associations between defective mismatch repair (MMR) and nucleotide excision repair (NER) and elevated microsatellite instability are linked to some human diseases, and are strong for hereditary nonpolyposis cancer. In contrast with their usual cellular functions, the excision repair systems can enhance the genetic instabilities of DNA repeats since they provide opportunities for non-B-DNA structures to form on single-stranded regions that are presented as the damage is excised from the DNA helix
From the earliest studies of natural DNAs, it became clear that repetitive DNA sequences are common, leading to expectations that there must be biological reasons to explain this
Summary
DNA molecules are the store of genetic information for all cellular organisms. The arrangements of individual bases in the DNA sequences of an organism, its genome, are specific to that organism, and elucidation of massive numbers of genome sequences have impacted on our understanding of the phylogenetic tree of life [1]. Simple repeats that are rich in G bases are often found at telomeric ends of chromosomes and there is significant evidence that such sequences form complexes of proteins bound to four-stranded structures [46]. Mononucleotide Cn sequences and repeats with Cn blocks are able to form hairpins (Figure 3B) and i-motif structures (Figure 3F) under conditions allowing the formation of hemi-protonated C+/C base pairs [47,48].
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