ATR 在逆转录病毒复制早期阶段的细胞上下文相关作用。
Cell context-dependent involvement of ATR in early stages of retroviral replication.
机构信息
Laboratory of retrovirology, University of Québec, 3351 boulevard des Forges, CP500, Trois-Rivières, QC, Canada.
出版信息
Virology. 2010 Jan 20;396(2):272-9. doi: 10.1016/j.virol.2009.10.032. Epub 2009 Nov 13.
Abstract
Retroviral DNA integration leaves behind a single-strand DNA discontinuity at each virus:host DNA junction. It has long been proposed that cellular proteins detect and repair the integrated DNA and that failure to do so might lead to apoptotic cell death, but their identity remains unknown. PIKK family members ATM, DNA-PKcs and ATR have all been proposed to be important for HIV-1 replication, but these findings turned out to be very controversial. In order to clarify their role in retroviral replication, we analyzed the effect of pharmacological inhibitors and of a dominant-negative version of ATR on the replication of retroviruses in cell lines relevant to HIV-1 infection. Our data show that ATR and probably other PIKKs as well are involved in retroviral replication in some but not all cell lines and that ATR increases the frequency of retroviral transduction by a mechanism other than the enhancement of infected cell survival.
摘要
逆转录病毒 DNA 整合会在每个病毒：宿主 DNA 连接处留下一条单链 DNA 不连续性。长期以来，人们一直认为细胞蛋白会检测和修复整合的 DNA，如果不能修复，可能会导致细胞凋亡死亡，但它们的身份仍然未知。PIKK 家族成员 ATM、DNA-PKcs 和 ATR 都被认为对 HIV-1 复制很重要，但这些发现结果却极具争议性。为了阐明它们在逆转录病毒复制中的作用，我们分析了药理学抑制剂和 ATR 的显性失活版本对与 HIV-1 感染相关的细胞系中逆转录病毒复制的影响。我们的数据表明，ATR 以及可能的其他 PIKKs 参与了某些细胞系而非所有细胞系中的逆转录病毒复制，ATR 通过增强受感染细胞存活以外的机制增加了逆转录病毒转导的频率。
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本文引用的文献
1
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2
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Cell Signal. 2009 Apr;21(4):509-22. doi: 10.1016/j.cellsig.2008.12.003. Epub 2008 Dec 24.
3
Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair.DNA修复之谜：MRN复合物和ATM激酶在DNA损伤修复中的作用
J Appl Genet. 2008;49(4):383-96. doi: 10.1007/BF03195638.
4
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Apoptosis. 2008 Sep;13(9):1088-99. doi: 10.1007/s10495-008-0239-0. Epub 2008 Jul 12.
5
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Nat Rev Mol Cell Biol. 2008 Aug;9(8):616-27. doi: 10.1038/nrm2450. Epub 2008 Jul 2.
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Clin Cancer Res. 2008 Mar 15;14(6):1877-87. doi: 10.1158/1078-0432.CCR-07-4298.
7
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DNA Repair (Amst). 2008 Apr 2;7(4):582-96. doi: 10.1016/j.dnarep.2007.12.012. Epub 2008 Mar 4.
8
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Toxicol Appl Pharmacol. 2008 May 15;229(1):20-32. doi: 10.1016/j.taap.2008.01.001. Epub 2008 Jan 17.
9
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Retrovirology. 2007 Sep 24;4:68. doi: 10.1186/1742-4690-4-68.
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