Single-stranded oligonucleotide-mediated gene repair in mammalian cells has a mechanism distinct from homologous recombination repair
Single-stranded oligonucleotide-mediated gene repair in mammalian cells has a mechanism distinct from homologous recombination repair
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DOI：
10.1016/j.bbrc.2006.09.078
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发表时间：
2006-11-24
影响因子：
3.1
通讯作者：
Huang, Han-Dong
中科院分区：
文献类型：
--
作者：
Wang, Zai;Zhou, Zhong-Jun;Huang, Han-Dong
单链DNA寡核苷酸（SSO）介导的基因修复在基因治疗和功能基因组学研究中具有巨大的潜力。然而，其潜在机制仍不清楚。来自其他小组的先前研究表明，通过ATM/ATR途径的DNA损伤反应可能参与了这一过程。在这项研究中，我们测量了两种ATM/ATR抑制剂咖啡因和喷替福林对SSO介导的基因修复的校正效率的影响。我们还检查了它们对双链断裂（DSB）诱导的同源重组修复（HRR）的影响作为对照，这是众所周知的依赖于ATM/ATR途径。我们发现这些抑制剂可以完全抑制DSB诱导的HRR，但只能部分抑制SSO介导的过程，表明SSO介导的基因修复不依赖于ATM/ATR通路。此外，我们发现胸苷处理促进SSO介导的基因修复，但抑制DSB诱导的HRR。总的来说，我们的研究结果表明，SSO介导的和DSB包含的基因修复有不同的机制。(c)2006年爱思唯尔公司All rights reserved.
Single-stranded DNA oligonucleotide (SSO)-mediated gene repair has great potentials for gene therapy and functional genomic studies. However, its underlying mechanism remains unclear. Previous studies from other groups have suggested that DNA damage response via the ATM/ATR pathway may be involved in this process. In this study, we measured the effect of two ATM/ATR inhibitors caffeine and pentoxifylline on the correction efficiency in SSO-mediated gene repair. We also checked their effect on double-stranded break (DSB)-induced homologous recombination repair (HRR) as a control, which is well known to be dependent on the ATM/ATR pathway. We found these inhibitors could completely inhibit DSB-induced HRR, but could only partially inhibit SSO-mediated process, indicating SSO-mediated gene repair is not dependent on the ATM/ATR pathway. Furthermore, we found that thymidine treatment promotes SSO-mediated gene repair, but inhibits DSB-induced HRR. Collectively, our results demonstrate that SSO-mediated and DSB-incluced gene repairs have distinct mechanisms. (c) 2006 Elsevier Inc. All rights reserved.