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Local structural transitions from the common B-DNA conformation into other DNA forms can be functionally important. This chapter describes the structures of DNA forms called alternative DNA conformations that are different from the canonical B-DNA helix. Also discussed are the requirements for the formation of alternative DNA structures, as well as their possible biological roles. The formation of non-B-DNA within certain sequence elements of DNA can be induced by changes in environmental conditions, protein binding and superhelical tension. Several lines of evidence indicate that alternative DNA structures exist in prokaryotic and eukaryotic cells. The data on their involvement in replication, gene expression, recombination and mutagenesis continues to accumulate.

DNA bending is universal in biology—both the storage and the retrieval of information encoded in the base-pair sequence require significant deformations, particularly bending, of the double helix. The A-tract curvature, which modulates these processes, has thus been a subject of long-standing interest. Here we describe the ongoing evolution of models developed to account for the sequence-dependent bending and curvature of DNA, namely the AA-wedge, junction, and flexible anisotropic dimer models. We further show that recent high-resolution NMR structures of DNA A-tracts are consistent with crystallographically observed structures, and that the combined data provide a realistic basis for describing the behavior of curved DNA in solution.

Intrinsically curved DNA structures often occur in or around origins of DNA replication, regions that regulate transcription, and DNA recombination loci, and are found in a wide variety of cellular and viral genomes from bacteria to man. In bacterial promoters, bent DNA structures are often located from immediately upstream of the −35 hexamer to around position −100 relative to the transcription start site (+1). They have a range of functions: facilitating RNA polymerase binding to the promoter, transition from closed to open promoter complexes, or transcription factor binding. To perform these functions, in some cases intrinsically curved structures function together with DNA bends that are induced by binding of RNA polymerase, transcription factors, or nucleoid-associated proteins. This chapter will describe how curved DNA structures are implicated in prokaryotic transcription.

Nucleoid-associated protein H-NS has emerged as one of the most intriguing and versatile global regulators of enterobacterial gene expression acting primarily yet not exclusively at the transcriptional level where it generally acts as a repressor. H-NS is also believed to contribute to the architectural organization of the nucleoid by causing DNA compaction, although the evidence for such a role is not overwhelming. H-NS binds preferentially to DNA elements displaying intrinsic curvatures and can induce DNA bending. These functions are determined by its quaternary tetrameric structure. In turn, the existence of an intrinsic DNA curvature separating two or more H-NS binding sites seems to be characteristic of the H-NS-sensitive promoters and a prerequisite for the transcriptional repressor activity of this protein. In some cases, like that of the promoter, the temperature-sensitivity of the DNA curvature represents a key element in the thermo-regulation of pathogenicity gene expression.

Intrinsically curved DNA structures are often found in or around transcriptional control regions of eukaryotic genes, and curved DNA may be common to all class I gene promoters. Although not all class II gene promoters contain curved DNA structures, both TATA-box-containing and TATA-box-less promoters often contain such structures. Furthermore, several studies have suggested that the TATA box itself adopts a curved DNA conformation. Curved DNA structures are likely to function in transcription in several ways. These include acting as a conformational signal for transcription factor binding; juxtaposition of the basal machinery with effector domains on upstream-bound factors; regulation of transcription in association with transcription-factor-induced bending of DNA; and organization of local chromatin structure to increase the accessibility of -DNA elements. This chapter presents a concise overview of studies of these functions.

In bacteria, RecA protein is indispensable for recombination, mutagenesis and for the induction of SOS genes. Curiously, anti-RecA antibodies recognize kin 17, a human nuclear Zn-finger protein of 45 kDa that preferentially binds to curved DNA and participates in a general response to diverse genotoxics. gene is conserved from yeast to man and codes for a protein involved in DNA replication. Recent observations suggest that kin 17 protein may also participate in RNA metabolism. Taken together all these data indicate the participation of kin 17 protein in a pathway that harmonizes transcription, replication and repair in order to circumvent the topological constraints caused by unusually complex lesions like multiply damaged sites.

Readout of eukaryotic genomes is soft-wired, leading to many different messages from a single gene. Z-DNA and double-stranded RNA (dsRNA) are both examples where genetic information is encoded by shape rather than by sequence. The use of these two conformational motifs to produce sequence-specific changes in RNA transcripts is discussed using dsRNA editing by ADAR1 as a model. This concept is extended to other RNA-directed modifications of DNA and RNA.

Certain DNA sequences preferentially adopt multistranded, non-B-form structures under physiological conditions. These include three-stranded DNA triplexes and four-stranded DNA quadruplexes. Several lines of evidence suggest that multiplex structures can form in vivo, either from the addition of oligonucleotides or through the transient formation of single-stranded regions. The consequences of multiplex structures on many DNA-dependent biological processes have been described. In this chapter I will review the effects of different DNA multiplexes on the process of transcription. The influence of parameters such as multiplex type and multiplex formation conditions on different transcription mechanistic steps in organisms spanning from prokaryotes to oocytes and mammalian cells will be discussed.

Fragile X mental retardation syndrome (FXS) and Friedreich ataxia (FRDA) belong to a group of genetic disorders known as the Repeat Expansion Diseases. These diseases all result from expansion of a specific tandem repeat. These repeats form a variety of secondary structures that have been suggested to play a role in this expansion. In addition, the properties of these structures suggest ways in which the expanded repeat could contribute to disease pathology. The FXS and FRDA repeats are transcribed but not translated, and expansion leads to aberrant transcription of the affected genes. This chapter discusses the types of nucleic acid structures formed by these repeats and their potential consequences for disease pathology.

Transcription and supercoiling of the template DNA are closely related each other. DNA supercoiling affects transcription and transcription affects supercoiling of the template DNA. Furthermore, packaging of genomic DNA into chromatin in eukaryotes raises another type of relation. DNA supercoiling can affect transcription through modulation of the chromatin structure.