Unusual Structures of the Tandem Repetitive DNA Sequences Located at Human Centromeres

Paolo Catasti, Lin Hong, Peter Yau, Goutam Gupta, Angel E. Garcia, Robert Ratliff, Robert K. Moyzis, E. Morton Bradbury

Research output: Contribution to journalArticlepeer-review

Abstract

The presence of the highly conserved repetitive DNA sequence d(AATGG)n·d(CCATT)n in human centromeres argues for a special role for this sequence in recognition, most probably through the formation of an unusual structure during mitosis. Quantitative one- and two-dimensional nuclear magnetic resonance (1D/2D NMR) spectroscopic studies reveal that the Watson-Crick duplex d(AATGG)n· d(CCATT)n adopts the usual B-DNA conformation as illustrated by taking d(AATGG)3·d(CCATT)3 as an example, whereas the d(CCATT)n strand is essentially a random coil. In contrast, the d(AATGG)n strand adopts an unusual stem-loop motif for repeat lengths n = 2, 3, 4, and 6. In addition to normal Watson-Crick A·T pairs, the stem-loop structures are stabilized by mismatched A·G and G·G pairs in the stem and G-G-A stacking in the loop. Stem-loop structures of d(AATGG)n are independently verified by gel electrophoresis and nuclease digestion studies and were also previously shown to be as stable as the corresponding Watson-Crick duplex d(AATGG)n·d(CCATT)n [Grady et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1695–1699]. Therefore, the sequence d(AATGG)n can, indeed, nucleate a stem-loop structure at little free energy cost, and if, during mitosis, it is located on the chromosome surface, it can provide specific recognition sites for kinetochore function.

Original languageEnglish (US)
Pages (from-to)3819-3830
Number of pages12
JournalBiochemistry
Volume33
Issue number13
DOIs
StatePublished - Apr 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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