Control of gene editing by manipulation of DNA repair mechanisms

被引:51
作者
Danner, Eric [1 ]
Bashir, Sanum [1 ,2 ]
Yumlu, Saniye [1 ,2 ]
Wurst, Wolfgang [3 ,4 ,5 ,6 ]
Wefers, Benedikt [3 ,4 ]
Kuehn, Ralf [1 ,2 ]
机构
[1] Max Delbruck Centrum Mol Med, Robert Rossle Str 10, D-13125 Berlin, Germany
[2] Berlin Inst Hlth, Kapelle Ufer 2, D-10117 Berlin, Germany
[3] Deutsch Zentrum Neurodegenerat Erkrankungen eV DZ, Feodor Lynen Str 17, D-81377 Munich, Germany
[4] Helmholtz Zentrum Munchen, Inst Dev Genet, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany
[5] Tech Univ Munchen Weihenstephan, Chair Dev Genet, Helmholtz Zentrum Munchen, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany
[6] Munich Cluster Syst Neurol SyNergy, Feodor Lynen Str 17, D-81377 Munich, Germany
关键词
STRAND BREAK REPAIR; HOMOLOGY-DIRECTED REPAIR; KNOCK-IN; END RESECTION; MOUSE MODEL; GENOME; CRISPR-CAS9; RECOMBINATION; 53BP1; DISTINCT;
D O I
10.1007/s00335-017-9688-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:262 / 274
页数:13
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