Journal
CELL CYCLE
Volume 7, Issue 15, Pages 2315-2320Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.6389
Keywords
intra-S checkpoint; replication stress; origin firing; elongation checkpoint; checkpoint in normal S phase
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Funding
- Research Council of Norway
- Norwegian Cancer Society
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In response to hydroxyurea treatment or DNA damage the total rate of DNA replication per cell is reduced. This reduction may be due to physical hindrance of the replication forks or to active, checkpoint-dependent processes. Here we review current knowledge about how and to what extent the intra-S checkpoint affects DNA replication. We discuss evidence that some checkpoint proteins are active even in a normal S phase and we suggest a model that resolves the apparent contradiction between different views on checkpoint-dependent slowing of the rate of DNA replication: does the intra-S checkpoint repress or delay the initiation of all origins or late replication origins only, and to what extent does it inhibit fork progression. Finally, the new model is discussed in the context of cancer development.
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