Abstract
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.
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Acknowledgements
The authors thank A. Wang for support with artwork. The author’s work is supported by the NIH (NIH/NCI CA093729 to K.M.V.).
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Related links
detectIR: https://sourceforge.net/projects/detectir/
DNA Structure Search: http://utw10685.utweb.utexas.edu/nonbdna/
G4Hunter: http://bioinformatics.ibp.cz
palindrome: http://emboss.bioinformatics.nl/cgi-bin/emboss/palindrome
QGRS Mapper: https://bioinformatics.ramapo.edu/QGRS/index.php
Glossary
- Circular dichroism
-
Absorption spectroscopy method to detect the differential absorption of left- and right-handed light spectra for rapid evaluation of the secondary structures of macromolecules such as protein and DNA.
- DNA helicases
-
A class of motor proteins that move along DNA and transiently separate duplexes into two single strands using energy from ATP hydrolysis.
- Fourier transform infrared spectroscopy
-
A spectroscopy method that simultaneously collects the absorption, emission and photoconductivity of a wide spectral range at high resolution to measure the intensity and wavelength of light required to vibrate molecules in a sample.
- Holliday junctions
-
Branched DNA structures containing four arms covalently linked together that serve as key intermediates in many meiotic and mitotic homologous recombination events.
- Negative supercoiling
-
A segment of underwound DNA in which the two strands wind around the helical axis less than 360° every 10.5 bp and retain twist strain (free energy).
- Okazaki fragments
-
Short fragments of DNA produced by discontinuous replication on the lagging strand during DNA replication. Because the template for lagging strand synthesis is exposed in the 5′–3′ direction at the progressing replication fork, the nascent strand is composed of sequential Okazaki fragments created by DNA polymerase working backwards from the replication fork.
- Satellites
-
A subfraction of genomic DNA consisting of short repetitive nucleotide sequences that are repeated a large number of times. These non-coding repeats are important for centromere and heterochromatin construction and separate from the rest of the genomic DNA on a density gradient because of their higher content of AT base pairs.
- SOS response
-
A complex global response to DNA damage identified in bacteria that includes activation of multiple factors, leading to the stalling of cell division and alteration of DNA replication, recombination and repair to promote genome integrity and cell survival, at the cost of increased mutagenesis.
- Stretching tension
-
When both ends of a segment of DNA are anchored (for example, by proteins) and the DNA is pulled mechanically, it carries stretching tension coupled with twisting torsion along the helix and can be elongated by up to 70% without disrupting base pairs.
- Topoisomerases
-
A class of enzymes that are able to cleave one or both strands of DNA to release topological stress on DNA duplex, and to link or unlink, knot or unknot associated DNA molecules.
- Translesion synthesis polymerases
-
Polymerases that can catalyse DNA polymerization at damaged templates during replication and/or repair, although often with lower fidelty than replicative polymerases.
- Unequal sister chromatid exchange
-
A mitotic crossover event that leads to the exchange of genetic material between homologous chromosomes and is also a major repair pathway for double-strand breaks.
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Wang, G., Vasquez, K.M. Dynamic alternative DNA structures in biology and disease. Nat Rev Genet 24, 211–234 (2023). https://doi.org/10.1038/s41576-022-00539-9
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DOI: https://doi.org/10.1038/s41576-022-00539-9
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