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Cell localization:[Isoform 2]: Nucleus. Isoform 10 is present throughout the cell.; [Isoform 4]: Nucleus.; [Isoform 7]: Nucleus.; [Isoform 9]: Nucleus.; [Isoform 12]: Nucleus.; Nucleus, PML body. Nucleus, nucleoplasm. Recruited into PML bodies together with TP53..In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutati
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