Dynamic alternative DNA structures in biology and disease

Repetitive elements in the human genome, once considered ‘junk DNA’, are now known to adopt more than a dozen alternative (that is, non-B) DNA structures, such as self-annealed hairpins, left-handed Z-DNA, three-stranded triplexes (H-DNA) or four-stranded guanine quadruplex structures (G4 DNA). These dynamic conformations can act as functional genomic elements involved in DNA replication and transcription, chromatin organization and genome stability. In addition, recent studies have revealed a role for these alternative structures in triggering error-generating DNA repair processes, thereby actively enabling genome plasticity. As a driving force for genetic variation, non-B DNA structures thus contribute to both disease aetiology and evolution. Non-B DNA secondary structures, such as G quadruplexes, H-DNA or Z-DNA, have key roles in genetic instability and disease aetiology. The authors review the impact of non-B DNA on transcription, replication, recombination and DNA damage and repair, the mechanisms of non-B DNA-induced mutagenesis and the role of non-B DNA sequences in human disease.