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  • Title: The radiation-induced S-phase checkpoint is independent of CDKN1A.
    Author: Guo CY, D'Anna JA, Li R, Larner JM.
    Journal: Radiat Res; 1999 Feb; 151(2):125-32. PubMed ID: 9952296.
    Abstract:
    We recently demonstrated that, in response to radiation, replication is down-regulated at the level of individual origins throughout S phase of the cell cycle. Since several in vitro studies demonstrate that CDKN1A (formerly known as p21) down-regulates replication by inhibiting PCNA, and since CDKN1A can retard progression of cells through S phase in vivo, the question arises whether CDKN1A is involved in the S-phase damage-sensing pathway. In the present study we analyzed the effect of ionizing radiation on CDKN1A+/+ and CDKN1A-/- cells derived from the HCT 116 cell line. Neither progression of cells through S phase nor survival after exposure to ionizing radiation is influenced by CDKN1A status in either synchronous or asynchronous cells. These results establish that CDKN1A is not necessary for the acute S-phase damage-sensing pathway that functions to prevent firing of replication origins during S phase.
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