Danner Eric, Bashir Sanum, Yumlu Saniye, Wurst Wolfgang, Wefers Benedikt, Kühn Ralf
Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Berlin Institute of Health, Kapelle-Ufer 2, 10117, Berlin, Germany.
Mamm Genome. 2017 Aug;28(7-8):262-274. doi: 10.1007/s00335-017-9688-5. Epub 2017 Apr 3.
DNA double-strand breaks (DSBs) are produced intentionally by RNA-guided nucleases to achieve genome editing through DSB repair. These breaks are repaired by one of two main repair pathways, classic non-homologous end joining (c-NHEJ) and homology-directed repair (HDR), the latter being restricted to the S/G2 phases of the cell cycle and notably less frequent. Precise genome editing applications rely on HDR, with the abundant c-NHEJ formed mutations presenting a barrier to achieving high rates of precise sequence modifications. Here, we give an overview of HDR- and c-NHEJ-mediated DSB repair in gene editing and summarize the current efforts to promote HDR over c-NHEJ.
DNA双链断裂(DSB)由RNA引导的核酸酶有意产生,以通过DSB修复实现基因组编辑。这些断裂通过两种主要修复途径之一进行修复,即经典非同源末端连接(c-NHEJ)和同源定向修复(HDR),后者仅限于细胞周期的S/G2期,且频率明显较低。精确的基因组编辑应用依赖于HDR,大量由c-NHEJ形成的突变对实现高比例的精确序列修饰构成了障碍。在这里,我们概述了基因编辑中HDR和c-NHEJ介导的DSB修复,并总结了目前促进HDR优于c-NHEJ的研究工作。