期刊
CELL CYCLE
卷 7, 期 15, 页码 2315-2320出版社
LANDES BIOSCIENCE
DOI: 10.4161/cc.6389
关键词
intra-S checkpoint; replication stress; origin firing; elongation checkpoint; checkpoint in normal S phase
类别
资金
- Research Council of Norway
- Norwegian Cancer Society
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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