Potential for H-DNA in the human MUC1 mucin gene promoter

Kristie L. Nelson, Nicole A. Becker, Gurcharan S. Pahwa, Michael A. Hollingsworth, L James Maher III

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Similar imperfect purine/pyrimidine mirror repeat (PMR) elements have previously been identified upstream of the human MUC1 mucin and CFTR genes. These elements confer S1 nuclease sensitivity on isolated plasmid DNA at low pH. We now present a detailed characterization of the non-B DNA structure responsible for S1 nuclease sensitivity upstream of the MUC1 gene. A ~90- base pair (bp) DNA fragment containing a 32-bp PMR element termed M-PMR3 was subcloned into a recombinant vector. This fragment conferred S1 nuclease sensitivity on the resulting supercoiled plasmid. High resolution mapping of sites reactive to S1 and P1 nucleases demonstrates that cleavage occurs within the M-PMR3 element. High resolution mapping with chemical agents selective for non-B DNA provides evidence that M-PMR3 adopts an H-DNA structure (intramolecular triple helix) in the less common H-y5 isomer at low pH. This result is observed in the presence or absence of Mg2+. Mutation of the native M-PMR3 element to create perfect homopurine/homopyrimidine mirror symmetry alters the preferred folding to the more common H-y3 triplex DNA isomer. These results demonstrate that imperfections in mirror symmetry can alter the relative stabilities of different H-DNA isomers.

Original languageEnglish (US)
Pages (from-to)18061-18067
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number30
DOIs
StatePublished - 1996

Fingerprint

Mucins
Mirrors
Genes
Isomers
DNA
Base Pairing
Plasmids
Chemical elements
Catalytic Domain
Defects
Mutation
triplex DNA
pyrimidine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Nelson, K. L., Becker, N. A., Pahwa, G. S., Hollingsworth, M. A., & Maher III, L. J. (1996). Potential for H-DNA in the human MUC1 mucin gene promoter. Journal of Biological Chemistry, 271(30), 18061-18067. https://doi.org/10.1074/jbc.271.30.18061

Potential for H-DNA in the human MUC1 mucin gene promoter. / Nelson, Kristie L.; Becker, Nicole A.; Pahwa, Gurcharan S.; Hollingsworth, Michael A.; Maher III, L James.

In: Journal of Biological Chemistry, Vol. 271, No. 30, 1996, p. 18061-18067.

Research output: Contribution to journalArticle

Nelson, KL, Becker, NA, Pahwa, GS, Hollingsworth, MA & Maher III, LJ 1996, 'Potential for H-DNA in the human MUC1 mucin gene promoter', Journal of Biological Chemistry, vol. 271, no. 30, pp. 18061-18067. https://doi.org/10.1074/jbc.271.30.18061
Nelson, Kristie L. ; Becker, Nicole A. ; Pahwa, Gurcharan S. ; Hollingsworth, Michael A. ; Maher III, L James. / Potential for H-DNA in the human MUC1 mucin gene promoter. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 30. pp. 18061-18067.
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