DNA 双链断裂处的 PI3K 样蛋白激酶成员 ATM 和 DNA-PKcs 的动态变化。
Dynamics of the PI3K-like protein kinase members ATM and DNA-PKcs at DNA double strand breaks.
机构信息
Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Cell Cycle. 2010 Jul 1;9(13):2529-36. doi: 10.4161/cc.9.13.12148.
Abstract
The protein kinases ATM and DNA-PKcs play critical roles in the cellular response to DNA double strand breaks (DSBs). ATM and DNA-PKcs are activated in response to DSBs and play several important roles in propagation of the damage signal and for the repair of DNA damage. Recent work from several groups, including ours, has focused on studying the dynamics of each of these proteins at DSBs and the requirements and factors which play a role(s) in this process. The use of live cell imaging of fluorescently-tagged ATM and DNA-PKcs has allowed us to study the real-time response of these proteins to laser-generated DNA damage in vivo. Here, we will extensively discuss the behavior of the ATM and DNA-PKcs proteins at DSB sites.
摘要
蛋白激酶 ATM 和 DNA-PKcs 在细胞对 DNA 双链断裂 (DSBs) 的反应中起着关键作用。ATM 和 DNA-PKcs 被激活以响应 DSBs，并在损伤信号的传播以及 DNA 损伤的修复中发挥几个重要作用。最近，包括我们在内的几个研究小组的工作重点是研究这两种蛋白质在 DSB 处的动力学，以及在这个过程中起作用的要求和因素。利用荧光标记的 ATM 和 DNA-PKcs 的活细胞成像，使我们能够在体内实时研究这些蛋白质对激光诱导的 DNA 损伤的反应。在这里，我们将广泛讨论 ATM 和 DNA-PKcs 蛋白在 DSB 位点的行为。
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J Cell Biol. 2009 Dec 28;187(7):977-90. doi: 10.1083/jcb.200906064. Epub 2009 Dec 21.
2
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J Biol Chem. 2010 Jan 8;285(2):1414-23. doi: 10.1074/jbc.M109.065615. Epub 2009 Nov 5.
3
Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining.
Biochem J. 2009 Feb 1;417(3):639-50. doi: 10.1042/BJ20080413.
4
DNA-PK: the means to justify the ends?
Adv Immunol. 2008;99:33-58. doi: 10.1016/S0065-2776(08)00602-0.
5
The Ku80 carboxy terminus stimulates joining and artemis-mediated processing of DNA ends.
Mol Cell Biol. 2009 Mar;29(5):1134-42. doi: 10.1128/MCB.00971-08. Epub 2008 Dec 22.
6
A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining.
J Clin Invest. 2009 Jan;119(1):91-8. doi: 10.1172/JCI37141. Epub 2008 Dec 15.
7
Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo.
J Cell Biol. 2008 Dec 1;183(5):777-83. doi: 10.1083/jcb.200805154.
8
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Cell. 2008 Oct 3;135(1):97-109. doi: 10.1016/j.cell.2008.08.017.
9
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