The emerging field of regenerative medicine is mainly approached by two different aspects. First is the use of stem cell based models to generate a suite of differentiated cells for therapeutic applications and the alternative approach is to utilize the non-mammalian models that have the inherent capacity to regenerate their...
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...
Full Text:
, and Cancer
Christopher K. 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...
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...
The accuracy of DNA synthesis depends on the accuracy of the polymerase as well as the quality and concentration(s) of the available 5'-deoxynucleoside-triphosphate DNA precursors (dNTPs). The relationships between dNTPs and error rates have been studied in vitro, but only limited insights exist into these correlations during in vivo replication....
Saccharomyces cerevisiae contains three NAD⁺/NADH kinases, one of which is localized in
mitochondria and phosphorylates NADH in preference to NAD⁺. Strand et al (Euk. Cell
2:809 (2003)) reported that a yeast mutation in POS5, which encodes the mitochondrial
NADH kinase, is a mutator, specific for mitochondrial genes. Because of the...
Deoxyribonucleoside triphosphate pools in mammalian mitochondria are highly
asymmetric, and this asymmetry probably contributes toward the elevated
mutation rate for the mitochondrial genome as compared with the nuclear
genome. To understand this asymmetry, we must identify pathways for synthesis
and accumulation of dNTPs within mitochondria. We have identified
ribonucleotide reductase...
Genomic instability drives tumorigenesis, but how it is initiated in sporadic neoplasias is unknown. In early preneoplasias, alterations at chromosome fragile sites arise due to DNA replication stress. A frequent, perhaps earliest, genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus, leading to loss of Fhit protein expression....
The down‐regulation of dominant oncogenes, including C‐MYC, in tumor cells often leads to the induction of
senescence via mechanisms that are not completely identified. In the current study, we demonstrate that MYC‐depleted
melanoma cells undergo extensive DNA damage that is caused by the underexpression of thymidylate synthase (TS) and
ribonucleotide...