細胞定位 |
Antigen Cellular Localization:
Nucleus. Nucleus, PML body Chromosome. Note=Depending on the cell type, it can also be found in PML nuclear bodies. Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling
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功能 |
Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication.
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總結 |
ATR (ATM and Rad3 related) is closely related to ATM (Ataxia telangiectasia, mutated) and is a member of the phosphatidylinositol 3 kinase (PI-3) family that is an early sensor of DNA damage. ATR is a serine-threonine kinase that reacts to UV damage and interruptions in replication. ATR may be able to sense DNA damage through interaction with Rad17 and 1as well as components of nucleosome remodeling complexes. In response to DNA damage, ATR has been shown to phosphorylate a multitude of substrates which include BRCA1, p53, Chk2, Rad 17, and E2F transcription factor 1.
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