Berman, H. M., Sussman, J. L., Joshua-Tor, L., Revich, G. G., Ripley, L. S. (1992) A structural model for sequence-specific proflavin-DNA interactions during in vitro frameshift mutagenesis. Journal of Biomolecular Structure and Dynamics, 10 (2). pp. 317-331. ISSN 07391102 (ISSN)
Abstract
Molecular models describing intermediates that may lead to proflavin- induced 1 bp deletions during in vitro polymerization by E. coli DNA polymerase I Klenow fragment are proposed. The models provide structural explanations for the fact that the induced frameshifts always occur opposite template bases that are adjacent to 5' pyrimidines and are based on the underlying hypothesis that the deletions arise because the polymerase passes by a template base without copying it. Because the most frequent mutations are opposite Pu in the template sequence 5' Py Pu 3', a single-strand loop- out model was constructed for this sequence and proflavin was added, using structures found in crystalline oligonucleotides and their complexes with proflavin. The model seeks to rationalize the roles of the 5' pyrimidine and proflavin in facilitating the bypass. Four potential roles for proflavin in mutagenesis are described: 1) stacking on the looped-out base; 2) stacking on the base pair immediately preceding the site of mutation; 3) hydrogen bonding with the 5' pyrimidine; 4) hydrogen bonding with the phosphate backbone. These models point to the possibility that a number of proflavin-DNA interactions may be involved. In contrast, modeling does not suggest a role for classically intercalated proflavin in frameshift mutagenesis arising during in vitro DNA polymerization.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | dna proflavine purine pyrimidine article base pairing chemical structure deletion mutant dna template drug dna interaction drug structure frameshift mutation hydrogen bond polymerization priority journal structure analysis Base Sequence Binding Sites DNA Polymerase I Escherichia coli Hydrogen Bonding Models, Molecular Molecular Sequence Data Mutagenesis Nucleic Acid Conformation Software |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > DNA polymerase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomal deletions |
| CSHL Authors: | |
| Communities: | CSHL labs > Joshua-Tor lab |
| Depositing User: | CSHL Librarian |
| Date: | 1992 |
| Date Deposited: | 20 Mar 2012 19:17 |
| Last Modified: | 17 Jan 2017 17:50 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/25508 |
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