For more than 35 years we have known that the accuracy of DNA replication is controlled in
large part by the relative concentrations of the four canonical deoxyribonucleoside 5'-triphosphates (dNTPs) at the replisome. Since this field was last reviewed, about eight years ago,
there has been increased understanding of the...
Cancer was recognized as a genetic disease at least four decades ago, with the realization that the spontaneous mutation rate must increase early in tumorigenesis, to account for the many mutations in tumor cells as compared with their progenitor normal cells. The genetic basis for cancer was established also from...
Full Text:
, and Cancer
ChristopherK. Mathews
Department of Biochemistry and Biophysics
Oregon State
Cancer was recognized as a genetic disease at least four decades ago, with the realization that the spontaneous mutation rate must increase early in tumorigenesis, to account for the many mutations in tumor cells as compared with their progenitor normal cells. The genetic basis for cancer was established also from...
Cancer was recognized as a genetic disease at least four decades ago, with the realization that the spontaneous mutation rate must increase early in tumorigenesis, to account for the many mutations in tumor cells as compared with their progenitor normal cells. The genetic basis for cancer was established also from...
One of the distinctive features of mitochondria is that they have their own DNA. When compared to nuclear DNA, it is known that mitochondrial DNA (mtDNA) not only has a much higher rate of spontaneous mutation, but also arises from metabolically distinct precursor pools. Others from our laboratory have demonstrated...
Ribonucleoside diphosphate reductase (RR) from vaccinia virus was recently cloned and overexpressed rn Escherichia coli. The amino acid sequence identities of the small and large subunits between the mouse and the vaccinia virus reductase are approximately 80 and 72 percent, respectively. In addition, vaccinia virus RR displays similar complex allosteric...
A crucial factor in determining the accuracy of DNA replication is
maintenance of a balanced supply of deoxyribonucleoside triphosphates
(dNTPs) at replication forks. Perturbation of dNTP biosynthesis can
induce dNTP pool imbalance with deleterious genetic consequences,
including increased mutagenesis, recombination, chromosomal
abnormalities and cell death. Using the T4 bacteriophage system,...
Bacteriophage T4 gene 42 encodes dCMP hydroxymethylase, an
enzyme unique to the deoxyribonucleotide metabolism of T-even
bacteriophages. To study biochemical and biophysical properties of
the enzyme, as well as the interaction of dCMP hydroxymethylase with
other DNA precursor biosynthetic enzymes in vitro, availability of large
amounts of the enzyme is...
The enzymes of dNTP synthesis in T4 infection associate to form a multienzyme complex, the T4 dNTP synthetase complex, facilitating the flow of metabolites en route to dNTPs, and their subsequent flow into DNA. Study of protein-protein interactions helps one to understand how the enzymes in the complex are organized...
Investigators have been studying an aggregate
containing enzymes of deoxyribonucleoside triphosphate
biosynthesis in T4-phage infected bacteria. They suggest
that it behaves as an organized complex, efficiently
channeling DNA precursors to the replication apparatus.
Previous work has suggested that about 10 enzyme
activities remain associated through several fractionation
steps. This multi-enzyme...