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DNA损伤反应与修复数据以及Tousled的药理学调节剂

DNA damage response and repair data with pharmacological modulators of Tousled.

作者信息

Timiri Shanmugam Prakash Srinivasan, Nair Renjith P, DeBenedetti Arrigo, Caldito Gloria, Abreo Fleurette, Sunavala-Dossabhoy Gulshan

机构信息

Department of Biochemistry and Molecular Biology, USA.

Department of Computational Biology and Bioinformatics, USA.

出版信息

Data Brief. 2016 Mar 30;7:1073-7. doi: 10.1016/j.dib.2016.03.075. eCollection 2016 Jun.

DOI:10.1016/j.dib.2016.03.075
PMID:27408917
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4927964/
Abstract

Human Tousled kinase 1 (TLK1) plays an important role in chromatin remodeling, replication, and DNA damage response and repair. TLK1 activity is immediately, but transiently, downregulated after genotoxic insult, and its recovery is important for exit from checkpoint arrest and cell survival after radiation. The data in this article compliments research presented in the paper titled, "Tousled kinase activator, gallic acid, promotes DNA repair and suppresses radiation cytotoxicity in salivary gland cells" [1]. The identification of small molecule activators and inhibitors of TLK1 provided an opportunity to pharmacologically alter the protein׳s activity to elucidate its role in DNA damage response pathways. TLK1 effectors, gallic acid (GA) and thioridazine (THD) activate and inhibit the kinase, respectively, and the data report on the impact of these compounds and the significance of TLK1 to DNA break repair and the survival of human salivary acinar cells.

摘要

人类Tousled激酶1(TLK1)在染色质重塑、复制以及DNA损伤反应与修复过程中发挥着重要作用。在基因毒性损伤后,TLK1的活性会立即但短暂地下调,其恢复对于辐射后从检查点阻滞状态退出以及细胞存活至关重要。本文中的数据补充了题为《Tousled激酶激活剂没食子酸促进唾液腺细胞DNA修复并抑制辐射细胞毒性》[1]的论文中所呈现的研究。TLK1小分子激活剂和抑制剂的鉴定为从药理学角度改变该蛋白的活性以阐明其在DNA损伤反应途径中的作用提供了契机。TLK1效应物没食子酸(GA)和硫利达嗪(THD)分别激活和抑制该激酶,并且本文数据报道了这些化合物的影响以及TLK1对人类唾液腺腺泡细胞DNA断裂修复和存活的重要性。

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本文引用的文献

1
Tousled kinase activator, gallic acid, promotes homologous recombinational repair and suppresses radiation cytotoxicity in salivary gland cells.蓬乱激酶激活剂没食子酸可促进唾液腺细胞的同源重组修复并抑制辐射细胞毒性。
Free Radic Biol Med. 2016 Apr;93:217-26. doi: 10.1016/j.freeradbiomed.2015.12.029. Epub 2016 Feb 15.
2
Recombinant AAV9-TLK1B administration ameliorates fractionated radiation-induced xerostomia.重组 AAV9-TLK1B 给药可改善分次放射治疗引起的口干症。
Hum Gene Ther. 2013 Jun;24(6):604-12. doi: 10.1089/hum.2012.235.
3
TAT-mediated delivery of Tousled protein to salivary glands protects against radiation-induced hypofunction.TAT 介导的 Tousled 蛋白转导至唾液腺可预防辐射诱导的功能低下。
Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):257-65. doi: 10.1016/j.ijrobp.2011.10.064. Epub 2012 Jan 26.
4
Adenoviral delivery of Tousled kinase for the protection of salivary glands against ionizing radiation damage.腺病毒介导的 Tousled 激酶转导对唾液腺免受电离辐射损伤的保护作用。
Gene Ther. 2011 Mar;18(3):275-82. doi: 10.1038/gt.2010.142. Epub 2010 Nov 4.
5
TLK1B promotes repair of DSBs via its interaction with Rad9 and Asf1.TLK1B 通过与 Rad9 和 Asf1 的相互作用促进 DSB 的修复。
BMC Mol Biol. 2009 Dec 20;10:110. doi: 10.1186/1471-2199-10-110.
6
Tousled homolog, TLK1, binds and phosphorylates Rad9; TLK1 acts as a molecular chaperone in DNA repair.蓬乱同源物TLK1与Rad9结合并使其磷酸化;TLK1在DNA修复中起分子伴侣的作用。
DNA Repair (Amst). 2009 Jan 1;8(1):87-102. doi: 10.1016/j.dnarep.2008.09.005. Epub 2008 Nov 5.
7
On the mechanism of salivary gland radiosensitivity.关于唾液腺放射敏感性的机制。
Int J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1187-94. doi: 10.1016/j.ijrobp.2004.12.051.
8
Suppression of Tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1.DNA损伤或复制受阻后,Tousled样激酶活性的抑制需要ATM、NBS1和Chk1。
Oncogene. 2003 Sep 4;22(38):5927-37. doi: 10.1038/sj.onc.1206691.
9
Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint.人源Tousled样激酶受ATM和Chk1依赖性DNA损伤检查点的靶向作用。
EMBO J. 2003 Apr 1;22(7):1676-87. doi: 10.1093/emboj/cdg151.