Journal
MOLECULAR CELL
Volume 11, Issue 2, Pages 341-351Publisher
CELL PRESS
DOI: 10.1016/S1097-2765(03)00037-6
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Funding
- NIGMS NIH HHS [1R01 GM55712, R01 -GM62281] Funding Source: Medline
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The S phase checkpoint protects the genome from spontaneous damage during DNA replication, although the cause of damage has been unknown. We used a dominant-negative mutant of a subunit of CAF-I, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S phase chromatin assembly and found that this induced S phase arrest. Arrest was accompanied by DNA damage and S phase checkpoint activation and required ATR or ATM kinase activity. These results show that in human cells CAF-I activity is required for completion of S phase and that a defect in chromatin assembly can itself induce DNA damage. We propose that errors in chromatin assembly, occurring spontaneously or caused by genetic mutations or environmental agents, contribute to genome instability.
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