Abstract
Many repetitive sequences in the human genome can adopt conformations that differ from the canonical B-DNA double helix (i.e., non-B DNA), and can impact important biological processes such as DNA replication, transcription, recombination, telomere maintenance, viral integration, transposome activation, DNA damage and repair. Thus, non-B DNA-forming sequences have been implicated in genetic instability and disease development. In this article, we discuss the interactions of non-B DNA with the replication and/or transcription machinery, particularly in disease states (e.g., tumors) that can lead to an abnormal cellular environment, and how such interactions may alter DNA replication and transcription, leading to potential conflicts at non-B DNA regions, and eventually result in genetic stability and human disease.
Highlights
Genomic DNA is the macromolecule responsible for the storage of genetic information; it is used for replicating another copy of genomic DNA for a daughter cell, and codes for other functional macromolecules such as messenger RNA for protein synthesis and regulatory non-coding RNAs in cells—i.e., DNA replication and transcription
We discovered that short repetitive sequences that can form H-DNA, Z-DNA or cruciform structures are intrinsically mutagenic in bacteria, yeast, mammalian cells and in mouse genomes [4,14,61,62,63]
We have summarized in review articles how non-B DNA conformations may be recognized as “DNA damage” and processed via DNA repair proteins in replication-dependent or replication-independent mechanisms [38,64]
Summary
Genomic DNA is the macromolecule responsible for the storage of genetic information; it is used for replicating another copy of genomic DNA for a daughter cell, and codes for other functional macromolecules such as messenger RNA for protein synthesis and regulatory non-coding RNAs in cells—i.e., DNA replication and transcription. Maintaining the accuracy and integrity of DNA is crucial for cell survival and, cells have developed highly sophisticated DNA damage-monitoring and repair systems to avoid mutation to maintain genome integrity. The distribution of mutations in human genomes is not random, and many mutational “hotspots” that have been identified in disease etiology are often located in specific repetitive, non-B DNA-forming sequences [1,2,3,4,5,6,7,8,9,10]
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