Intrinsically unstable life of DNA triplet repeats associated with human hereditary disorders

Bowater, Richard P. ORCID: and Wells, Robert D. (2001) Intrinsically unstable life of DNA triplet repeats associated with human hereditary disorders. Progress in Nucleic Acid Research and Molecular Biology, 66. pp. 159-202.

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Expansions of specific DNA triplet repeats are the cause of an increasing number of hereditary neurological disorders in humans. In some diseases, such as Huntington's and several spinocerebellar ataxias, the repetitive DNA sequences are translated into long tracts of the same amino acid (usually glutamine), which alters interactions with cellular constituents and leads to the development of disease. For other disorders, including common genetic disorders such as myotonic dystrophy and fragile X syndrome, the DNA repeat is located in noncoding regions of transcribed sequences and disease is probably caused by altered gene expression. In studies in lower organisms, mammalian cells, and transgenic mice, high frequencies of length changes (increases and decreases) occur in long DNA triplet repeats. These observations are similar to other types of repetitive DNA sequences, which also undergo frequent length changes at genomic loci. A variety of processes acting on DNA influence the genetic stability of DNA triplet repeats, including replication, recombination, repair, and transcription. It is not yet known how these diffirent multienzyme systems interact to produce the genetic mutation of expanded repeats. In vitro studies have identified that DNA triplet repeats can adopt several unusual DNA structures, including hairpins, triplexes, quadruplexes, slipped structures, and highly flexible and writhed helices. The formation of stable unusual structures within the cell is likely to disturb DNA metabolism and be a critical intermediate in the molecular mechnism(s) leading to genetic instabilities of DNA repeats and, hence, to disease pathogenesis.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Molecular Microbiology
Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Depositing User: EPrints Services
Date Deposited: 01 Oct 2010 13:37
Last Modified: 16 Jul 2024 13:30
DOI: 10.1016/S0079-6603(00)66029-4

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