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Science 2 April 1999:
Vol. 284. no. 5411, pp. 159 - 162
DOI: 10.1126/science.284.5411.159
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Reports
Phenotypic Change Caused by Transcriptional Bypass of Uracil in Nondividing Cells
Anand Viswanathan,
12
Ho Jin You,
2
Paul W. Doetsch
2*
Cytosine deamination to uracil occurs frequently in cellular DNA.
In vitro, RNA polymerase efficiently inserts adenine opposite to
uracil, resulting in G to A base substitutions. In vivo, uracil could
potentially alter transcriptional fidelity, resulting in production of
mutant proteins. This study demonstrates that in nondividing
Escherichia coli cells, a DNA template base replaced with
uracil in a stop codon in the firefly luciferase gene results in
conversion of inactive to active luciferase. The level of
transcriptional base substitution is dependent on the capacity to
repair uracil. These results provide evidence for a DNA
damage-dependent, transcription-driven pathway for generating mutant
proteins in nondividing cells.
1 Graduate Program in Genetics and Molecular
Biology and
2 Departments of Biochemistry and
Radiation Oncology, Emory University School of Medicine, Atlanta, GA
30322, USA.
*
To whom correspondence should be addressed. E-mail:
medpwd{at}emory.edu
Read the Full Text
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