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Title: Identification of modified bases and their locations in DNA

Thesis/Dissertation ·
OSTI ID:5402170

I. The locations of modified and common bases in an oligodeoxyribonucleotide may be determined by a simple two-dimensional separation on a polyethyleneimine-cellulose thin layer sheet. Chromatography in the first dimension fractionates by chain length a nested set of fragments that are generated by subjecting the oligomer to partial spleen phosphodiesterase degradation followed by labelling their non-common ends with /sup 32/P using polynucleotide kinase. A subsequent in situ treatment with nuclease Bal 31 produces labelled mononucleotides, and these are identified by chromatography in the second dimension. Since the method does not identify the 3' terminal nucleotide, a convenient procedure involving 3' end labelling followed by enzymatic digestion to monomers has been developed for this purpose. II. A two-dimensional method which can be used to conjunction with a standard sequencing technique to identify the positions of modified bases in polydeoxyribonucleotides is described. In the first dimension, a set of DNA fragments is separated by length, and in the second dimension, the 5' termini are identified. Autoradiography then shows a pattern of spots corresponding to the nucleotides, including those with modified bases, at each position of the polynucleotide chain. In case the resolution of the spots after the two-dimensional separation does not allow precise location of a particular base, comparison of the autoradiograph with the sequence as determined by a standard technique allows the location to be determined without ambiguity.

Research Organization:
Purdue Univ., Lafayette, IN (USA)
OSTI ID:
5402170
Resource Relation:
Other Information: Thesis (Ph. D.)
Country of Publication:
United States
Language:
English