Tetraplex DNA and its interacting proteins

Mounting evidence indicates that certain nucleotide sequences impose non-canonical secondary structures on DNA. The resulting variable conformations are thought to bestow on the DNA informational content additional to that encoded by its linear arrangement of bases. DNA sequences that include clusters of contiguous guanine residues readily form in vitro diverse types of four-stranded structures collectively named tetraplex or quadruplex DNA. Data suggest that tetraplex DNA structures are likely to be formed in vivo and to have roles in key biological processes such as regulation of gene transcription, maintenance of telomeres, DNA recombination and the packaging of retroviral genome. A credible argument for the existence of quadruplex DNA in vivo is the prevalence of numerous viral and cellular proteins that interact physically and functionally with tetrahelical DNA. Some such proteins bind selectively and tightly to tetraplex DNA, others promote the formation of DNA tetrahelices or act to unwind them, and several nucleases cleave tetraplex DNA preferentially. The protein-mediated structural transformations of quadruplex DNA and its selective nucleolytic cleavage argue strongly for transient formation of tetrahelical DNA in the cell. This review surveys tetraplex structures of DNA and their interacting proteins and appraises the evidence for their biological roles.