Inhibition of telomerase by G-quartet DNA structures

The ends or telomeres of the linear chromosomes of eukaryotes are composed of tandem repeats of short DNA sequences, one strand being rich in guanine (G strand) and the complementary strand in cytosine. Telomere synthesis involves the addition of telomeric repeats to the G strand by telomere termina...

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Bibliographic Details
Published in:Nature (London) 1991-04, Vol.350 (6320), p.718-720
Main Authors: ZAHLER, A. M, WILLIAMSON, J. R, CECH, T. R, PRESCOTT, D. M
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological and medical sciences
Chromatin. Chromosome
DNA Nucleotidylexotransferase - antagonists & inhibitors
DNA, Protozoan - genetics
Eukaryota - enzymology
Eukaryota - physiology
Fundamental and applied biological sciences. Psychology
Kinetics
Molecular and cellular biology
Molecular genetics
Nucleic Acid Conformation
Oligodeoxyribonucleotides - pharmacology
Potassium - pharmacology
Repetitive Sequences, Nucleic Acid
Sodium - pharmacology
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Summary:The ends or telomeres of the linear chromosomes of eukaryotes are composed of tandem repeats of short DNA sequences, one strand being rich in guanine (G strand) and the complementary strand in cytosine. Telomere synthesis involves the addition of telomeric repeats to the G strand by telomere terminal transferase (telomerase). Telomeric G-strand DNAs from a variety of organisms adopt compact structures, the most stable of which is explained by the formation of G-quartets. Here we investigate the capacity of the different folded forms of telomeric DNA to serve as primers for the Oxytricha nova telomerase in vitro. Formation of the K(+)-stabilized G-quartet structure in a primer inhibits its use by telomerase. Furthermore, the octanucleotide T4G4, which does not fold, is a better primer than (T4G4)2, which can form a foldback structure. We conclude that telomerase does not require any folding of its DNA primer. Folding of telomeric DNA into G-quartet structures seems to influence the extent of telomere elongation in vitro and might therefore act as a negative regulator of elongation in vivo.
ISSN:0028-0836
1476-4687
DOI:10.1038/350718a0