抑制非同源末端连接并不能挽救范可尼贫血症患者细胞的 DNA 修复缺陷。
Suppression of non-homologous end joining does not rescue DNA repair defects in Fanconi anemia patient cells.
机构信息
Laboratory of Genome Maintenance, The Rockefeller University , New York, NY, USA.
出版信息
Cell Cycle. 2020 Oct;19(19):2553-2561. doi: 10.1080/15384101.2020.1810394. Epub 2020 Aug 30.
Abstract
Severe cellular sensitivity and aberrant chromosomal rearrangements in response to DNA interstrand crosslink (ICL) inducing agents are hallmarks of Fanconi anemia (FA) deficient cells. These phenotypes have previously been ascribed to inappropriate activity of non-homologous end joining (NHEJ) rather than a direct consequence of DNA ICL repair defects. Here we used chemical inhibitors, RNAi, and Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas9 to inactivate various components of NHEJ in cells from FA patients. We show that suppression of DNA-PKcs, DNA Ligase IV, and 53BP1 is not capable of rescuing ICL-induced proliferation defects and only knockout partially suppresses the chromosomal abnormalities of FA patient cells.
摘要
严重的细胞敏感性和异常的染色体重排，是对 DNA 链间交联（ICL）诱导剂反应的范可尼贫血（FA）缺陷细胞的特征。这些表型以前归因于非同源末端连接（NHEJ）的不适当活性，而不是 DNA ICL 修复缺陷的直接后果。在这里，我们使用化学抑制剂、RNAi 和规律成簇间隔短回文重复（CRISPR）-Cas9 来使 FA 患者细胞中的 NHEJ 的各种成分失活。我们表明，抑制 DNA-PKcs、DNA 连接酶 IV 和 53BP1 不能挽救 ICL 诱导的增殖缺陷，只有 knockout 部分抑制 FA 患者细胞的染色体异常。
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