Thymidine-analog mutations

TK is an enzyme that allows cells to take up thymidine from the surrounding medium for incorporation into the DNA. Specifically for this assay, the TK phenotype is used. If a thymidine analog were added to suspension or soft agar, it would eventually be incorporated into the DNA, thereby resulting in the death of the cell. Cells deficient in thymidine kinase (TK ) due to the mutation (Tk+ are resistant to the cytotoxic ef-... 

Mechanisms Stavudine is a thymidine analog. Depending on specific sites of mutation on the reverse transcriptase gene, resistance may emerge to stavudine alone, or cross-resistance between other NRTIs may occur. 

One way in which chemical compounds can induce base substitution mutation is through their incorporation into the structure of DNA itself. Thus, 5-bromodeoxyuridine (or bromouracil) can replace thymidine in DNA, where it serves as an efficient mutagenic agent.767 2-Aminopurine, an analog of adenine, pairs with thymine, just as does adenine when incorporated into DNA. 

In HeLa ceils hydroxyurea is an efficient inhibitor of histone synthesis. This action requires protein synthesis and leads to rapid disappearance of cytoplasmatic histone mRNA The effect is not specific for hydroxyurea since suppression of DNA synthesis by arabino-cytosine or temperature-sensitive mutations yields analogous results. Similarly, the synthesis of some enzymes necessary for DNA replication and active in S-phase is altered by hydroxyurea. Increased activity of ribonucleotide reductase in HeLa and in hamster cells and of the salvage enzyme thymidine kinase in HeLa cells and KB cells has been observed, probably as a consequence of the increased fraction of cells in S-phase. Repression occurs for thymidine kinase in human lymphocytes and for ornithine decarboxylase in Chinese hamster fibroblasts whereas no or only slight effects were seen on ribonucleotide reductase in hamster fibroblasts , on thymidylate synthase in extracts from synchronous mouse cells " , and on DNA polymerase in rabbit kidney cells or HeLa cells . ... 

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