| 背景 | Serine/threonine-protein kinase ATR is a ~301 kDa protein. 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, RBBP8, 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 at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. 1. Hall-Jackson, CA. et al. (1999) Oncogene 18, 6707-13. PMID: 105972772. Kim, ST. et al. (1999) The Journal of biological chemistry 274, 37538-43. PMID: 106088063. Liu, Q. et al. (2000) Genes & development 14, 1448-59. PMID: 108591644. Cortez, D. et al. (2001) Science (New York, N.Y.) 294, 1713-6. PMID: 117210545. Zou, L. et al. (2003) Science (New York, N.Y.) 300, 1542-8. PMID: 127919856. Barr, SM. et al. (2003) Current biology : CB 13, 1047-51. PMID: 128145517. Wang, Y. et al. (2003) Proceedings of the National Academy of Sciences of the United States of America 100, 15387-92. PMID: 146573498. Unsal-Kaçmaz, K. et al. (2004) Molecular and cellular biology 24, 1292-300. PMID: 147299739. Ward, IM. et al. (2004) The Journal of biological chemistry 279, 9677-80. PMID: 1474243710. Cortez, D. et al. (2004) Proceedings of the National Academy of Sciences of the United States of America 101, 10078-83. PMID: 15210935 |
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