Transient inhibition of DNA synthesis results in increased dihydrofolate reductase synthesis and subsequent increased DNA content per cell.
AUTOR(ES)
Johnston, R N
RESUMO
We examined the role that blockage of cells in the cell cycle may play in the stimulation of gene amplification and enhancement of drug resistance. We found that several different inhibitors of DNA synthesis, which were each able to block cells at the G1-S-phase boundary, induced an enhanced cycloheximide-sensitive synthesis of an early S-phase cell cycle-regulated enzyme, dihydrofolate reductase, and of other proteins as well. This response was specific, in that blockage at the G2 phase did not result in overproduction of the enzyme. When the cells were released from drug inhibition, DNA synthesis resumed, resulting in a cycloheximide-sensitive elevation in DNA content per cell. We speculate that the excess DNA synthesis (which could contribute to events detectable later as gene amplification) is a consequence of the accumulation of S-phase-specific proteins in the affected cells, which may then secondarily influence the pattern of DNA replication.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=367083Documentos Relacionados
- Single-molecule and transient kinetics investigation of the interaction of dihydrofolate reductase with NADPH and dihydrofolate
- Inhibition of mitochondrial protein synthesis results in increased endothelial cell susceptibility to nitric oxide-induced apoptosis
- Increased Dihydrofolate Reductase Synthesis in DIPLOCOCCUS PNEUMONIAE following Translatable Alteration of the Structural Gene. I. Genotype Derivation and Recombinational Analyses
- Increased synthesis of ribonucleotide reductase after deoxyribonucleic acid inhibition in various species of bacteria.
- High Dihydrofolate Reductase Levels in Diplococcus pneumoniae After Mutation in the Structural Gene: Biochemical and Immunological Evidence for Increased Synthesis