Lawrence C. Sowers
University of Southern California
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Featured researches published by Lawrence C. Sowers.
Mutation Research | 1987
Lawrence C. Sowers; Barbara Ramsay Shaw; Martina L. Veigl; W. David Sedwick
The nature of hydrogen bonding between normal and modified bases has been re-examined. It is proposed that hydrogen-bonding schemes may involve tautomeric, ionized or conformational forms (syn, anti and wobble). Several important cases are presented or reviewed in which physical evidence indicates the existence of ionized base pairs. When thermodynamic values determined in aqueous solution under physiological conditions are considered, it can be argued that base ionization will contribute substantially to the stability of many biologically relevant base pairs containing modified bases. A significant incidence of ionized bases in DNA may have important kinetic ramifications for the further chemical reactivity of both the modified base and its cross-strand pairing partner. Moreover, DNA structure at and surrounding ionized base pairs may be altered. For this reason, the model presented in this study should be useful as DNA-sequence analysis becomes more commonly applied to the study of mutagenesis.
Journal of Molecular Biology | 1989
Lawrence C. Sowers; Myron F. Goodman; Ramon Eritja; Bruce E. Kaplan; G.V. Fazakerley
A one and two-dimensional nuclear magnetic resonance study of a non-selfcomplementary oligonucleotide containing a central 5-bromouracil-guanine pair is reported. For these two bases three types of hydrogen bonding schemes could exist; wobble, rare tautomer and ionized. The two-dimensional spectra of non-exchangeable protons together with one-dimensional spectra recorded in water show that at pH 7.0 the predominant species is a right-handed B-form DNA in which the brU.G pair has wobble geometry. On raising the pH we observe a transition monitored by proton chemical shift changes for the brU.G and adjacent base-pairs. The mid-point of the transition was observed at pH 8.6. Spectra recorded at pH 9.8 show that the helix remains intact with B form conformation. It is shown that this high pH form has an ionized brU.G base-pair now in Watson-Crick geometry. Thus under physiological conditions an equilibrium exists between wobble and ionized structures.
Biochemical and Biophysical Research Communications | 1987
Thomas A. Hardy; David J. Baker; Edward M. Newman; Lawrence C. Sowers; Myron F. Goodman; Steven S. Smith
M13 DNAs in which carbon 5 of each deoxycytidine residue in one strand is replaced with a bulky group are very good substrates for human DNA (cytosine-5) methyltransferase. Rate enhancements of up to 35 fold are obtained depending on the size of the moiety at C-5. The enzyme appears optimally suited to sense a methyl group in one strand at this position. Alkaline density gradient analyses of the distribution of methyl groups applied to 5-BrdCyd or 5-IdCyd substituted DNA reveal that these groups serve to direct the enzyme to methylate the unsubstituted strand.
Nucleosides, Nucleotides & Nucleic Acids | 1989
Lawrence C. Sowers; Dhananjaya N. Mhaskar; Tasneem A. Khwaja; Myron F. Goodman
Abstract We report the synthesis of N-15 enriched 2-aminopurine-2′-deoxynucleoside (APdR). Both ring and 2-amino nitrogens were labelled via a Dimroth rearrangement of the free base. The corresponding deoxynucleoside was prepared enzymatically. Results of both proton and N-15 NMR studies show that the predominant tautomeric form of APdR is amino and the N1 position is shown to be the site of protonation.
Journal of Biomolecular Structure & Dynamics | 1987
G.V. Fazakerley; Lawrence C. Sowers; Ramon Eritja; Bruce E. Kaplan; Myron F. Goodman
We have synthesized and studied by proton NMR a duplex heptaoligonucleotide containing a 5-bromouracil (brU)-adenine base pair. This represents the first structural characterization of a B-form DNA containing brU. The brU.A base pair is Watson-Crick rather than Hoogsteen as seen for the monomers in the crystalline state. From analysis of the NOESY sepctra at very short mixing times evidence is presented that substitution of brU for T induces significant conformational changes from that of a normal B DNA. The helix twist between brU4.A11 and G3.C12 is ca. 15 degrees and for both brU4 and G3 the glycosyl torsion angles are significantly changed. The imino proton of the bru.A base pair shows a pH insensitive line with which shows that the pK of brU in this base pair is very much higher than that of the monomer.
Proceedings of the National Academy of Sciences of the United States of America | 1988
John Petruska; Myron F. Goodman; M. S. Boosalis; Lawrence C. Sowers; Chaejoon Cheong; Ignacio Tinoco
Proceedings of the National Academy of Sciences of the United States of America | 1986
Lawrence C. Sowers; G.V. Fazakerley; Ramon Eritja; Bruce E. Kaplan; Myron F. Goodman
Proceedings of the National Academy of Sciences of the United States of America | 1986
John Petruska; Lawrence C. Sowers; Myron F. Goodman
Proceedings of the National Academy of Sciences of the United States of America | 1999
Wu Suen; Thomas G. Spiro; Lawrence C. Sowers; Jacques R. Fresco
Journal of Biological Chemistry | 1988
Lawrence C. Sowers; Ramon Eritja; B Kaplan; Myron F. Goodman; G V Fazakerly