Radiation down-regulates replication origin activity throughout the S phase in mammalian cells
| Autor: | Hoyun Lee, Carl L. Schildkraut, Joyce L. Hamlin, P A Dijkwel, Randall D. Little, James M. Larner |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
DNA damage
Period (gene) Down-Regulation Replication Origin Biology Origin of replication DNA Ribosomal Cell Line S Phase chemistry.chemical_compound Hepatolenticular Degeneration Genetics medicine Animals Humans Electrophoresis Gel Two-Dimensional Replicon Repetitive Sequences Nucleic Acid DNA replication medicine.disease Molecular biology chemistry Gamma Rays Cell culture Ataxia-telangiectasia DNA Research Article |
| Zdroj: | Nucleic Acids Research. 27:803-809 |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/27.3.803 |
| Popis: | An asynchronous culture of mammalian cells responds acutely to ionizing radiation by inhibiting the overall rate of DNA replication by approximately 50% for a period of several hours, presumably to allow time to repair DNA damage. At low and moderate doses, this S phase damage-sensing (SDS) pathway appears to function primarily at the level of individual origins of replication, with only a modest inhibition of chain elongation per se. We have shown previously that the majority of the inhibition observed in an asynchronous culture can be accounted for by late G1cells that were within 2-3 h of entering the S period at the time of irradiation and which then fail to do so. A much smaller effect was observed on the overall rate of replication in cells that had already entered the S phase. This raised the question whether origins of replication that are activated within S phase per se are inhibited in response to ionizing radiation. Here we have used a two-dimensional gel replicon mapping strategy to show that cells with an intact SDS pathway completely down-regulate initiation in both early- and late-firing rDNA origins in human cells. We also show that initiation in mid- or late-firing rDNA origins is not inhibited in cells from patients with ataxia telangiectasia, confirming the suggestion that these individuals lack the SDS pathway. |
| Databáze: | OpenAIRE |
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