Laboratory of Genome Editing, Federal State Budgetary Institution "Research Centre for Medical Genetics", Moskvorechie, 1, Moscow, Russia, 115522.
Mol Biol Rep. 2020 Mar;47(3):2371-2379. doi: 10.1007/s11033-020-05285-x. Epub 2020 Feb 8.
The majority of CRISPR-Cas9 methods for mutations correction are oriented on gene editing through homologous recombination that is normally restrained by non-homologous end joining (NHEJ). A recently identified protein TIRR can bind a 53BP1 protein, a key effector of NHEJ, and inhibit its recruitment to double-strand break loci. Several studies elucidated the molecular mechanisms of TIRR-53BP1 binding and established bidirectional role of TIRR in 53BP1 functions and stability. It was proved that overexpression of TIRR promotes the double-strand break repair through homologous recombination. All findings, which were described in the review, allow assuming TIRR as a suitable target for enhancing efficacy of genome editing through homology directed repair.
大多数用于突变校正的 CRISPR-Cas9 方法都针对通过同源重组进行基因编辑，而同源重组通常受到非同源末端连接 (NHEJ) 的限制。最近发现的一种蛋白质 TIRR 可以结合 NHEJ 的关键效应因子 53BP1 蛋白，并抑制其募集到双链断裂部位。几项研究阐明了 TIRR-53BP1 结合的分子机制，并确定了 TIRR 在 53BP1 功能和稳定性中的双向作用。已经证明，TIRR 的过表达可促进通过同源重组进行双链断裂修复。综述中描述的所有发现都使 TIRR 成为通过同源定向修复提高基因组编辑效率的合适靶标。
