Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks
Abstract
:1. Introduction
2. The Mechanism of DSB Repair Used by the CRISPR/Cas9 System
2.1. HDR
2.2. NHEJ/c-NHEJ
2.3. Two Additional Pathways
3. The Mechanism Regulating the Choice between the HDR and NHEJ Repair Pathways
3.1. The Regulation of DNA Resection by Cyclin-Dependent Kinases
3.2. The Regulation of DNA Resection by Ubiquitin
3.3. The Battle between 53BP1 and BRCA1 for DNA Resection
4. Methods to Enhance CRISPR/Cas9-Mediated HDR Choice
4.1. Regulation of the Trade-Off between c-NHEJ and HDR
4.1.1. Suppression of Key NHEJ Factors
4.1.2. In Favor of HDR Factors
4.1.3. Manipulation of the Relationship between 53BP1 and BRCA1
4.2. Cas9 Activity Paired with the HDR-Active Cell Cycle Phase
4.3. All the Components in One HDR Complex
5. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Target | Treatment | HDR Increasement | Cell Type | Gene Locus | Editing Type | Ref. |
---|---|---|---|---|---|---|
DNA Ligase IV inhibitor | SCR7 | 3-fold | A549 | TSG101 | Stop cassette KI | [80] |
19-fold | Mel-JuSo | TSG101 | Stop cassette KI | [80] | ||
13-fold(4.58–58.3%) | DC2.4 | Tap1 | Venus KI fluorescent gene KI | [80] | ||
4.5-fold(5–22.7%) | Mouse zygotes | Igk | LPETG KI | [80] | ||
5-fold(5–25%) | HEK293 | AAVS1-TLR | GC | [82] | ||
10-fold(5.8–56.2%) | Mouse embryos | Tex1 | GC | [81] | ||
2.5-fold(2.7–6.6%) | MCF-7 | AAVS | GC | [85] | ||
10-fold(1.1–4.3%) | HCT-116 | AAVS | MCS KI | [85] | ||
4-fold (5.6–11.2%) | Porcine fetal fibroblasts | eGFP | MCS KI | [86] | ||
1.9-fold (26.22–49.66%) | Primary porcine cell | ROSA26 | Neomycin KI | [86] | ||
3.5-fold (1.9–6.6%) | MCF-7 /GFP-mut | - | GC | [86] | ||
1.7-fold (8.4–14.6%) | HCT-116 ΔTCT | β-catenin | GC | [86] | ||
3.7-fold (15–55%) | Zebrafish embryos | Ybx 1 | S82A GC | [83] | ||
2.2-fold (18–39%) | Rat zygotes | Fabp2 | Cre KI | [84] | ||
1.4-fold (46–64%) | Rat zygotes | Dbndd | Cre ER T2 KI | [84] | ||
NS | Rabbit embryos | RLL | EGFP KI | [87] | ||
NS | HEK-293T | rOSA26 | Neomycin KI resistance gene KI | [88] | ||
NS | Porcine foetal Fibroblasts | Rosa26 | EGFP KI | [89] | ||
NS | HSPC | Rosa26 | EGFP KI | [90] | ||
NS | U2OS | LMNA-GFP | GC | [91] | ||
NS | HEK-293T | GAPDH | HIBIT KI | [92] | ||
PK-cs inhibitor | NU7441 | 3~9-fold | MEF | TP53 | GC | [95] |
2-fold (1.9–3.8%) | HEK293-TLR | - | GC | [95] | ||
13.5-fold (4–53%) | Zebra embryos | - | mCherry KI | [96] | ||
2.5-fold (8.6–21.5%) | A549 | CD45 | GFP KI | [90] | ||
2.4-fold (8–19.2%) | CD34+ HSPC | CD45 gene/GFP insertion | GFP KI | [90] | ||
1.3-fold (4.6–6%) | U2OS | LMNA | mClover KI insertion | [91] | ||
KU-0060648 | 2~8–fold | MEF | TP53 | GC | [95] | |
2.2-fold (1.9–4.1%) | HEK293-TLR | - | GC | [95] | ||
NU7026 | 1.6-fold (3.7–6.0%) | iPSCs | AAVS | KI | [97] | |
1.7-fold (19–32%) | hiPSCs-409B2 | FRMD7 | GC | [98] | ||
2.4-fold (2.5–6%) | HEK293 | GFP | KI | [130] | ||
M3814 | 4-fold (18–81%) | K562 cells-409B2 hiPSCs | FRMD7 | GC | [98] | |
Rad51 agonist | RS-1 | EP 3-fold(2.5–7.5%)epEP/electroporation | HEK293A | LMNA | Clover KI | [101] |
Lipo 6-fold(3.5–21%)/lipofection | HEK293A | LMNA | Clover KI | [101] | ||
8.5-fold (0.8–6.8%) | Rabbit embryos | RLL | EGFP KI | [87] | ||
2.1-fold (8–16.8%) | CD34+ HSPC | CD45 gene/GFP insertion | GFP KI | [90] | ||
1.6-fold(15–24%) | Zebrafish embryos | Ybx1 | S82A GC | [83] | ||
NS | iPSC | CTNB1/PRDM14 | mNeoGreen KI | [97] | ||
Cell cycle Synchronization | Nocodazole | 2.2-fold(9–20%) | HEK293T | EMX1, DYRK1 | MCS KI | [116] |
1.7-fold (13–22%) | iPSC | PRDM14 | mCherry KI | [131] | ||
1.7-fold (7–12%) | iPSC | CTNNB | mCherry KI | [131] | ||
1.4-fold (14–19.2%) | HEK293T | MALAT1 | MCS KI | [88] | ||
6.7-fold (7.86–52.49%) | DiPSC | NEUROD | Puromycin KI | [117] | ||
3.4-fold (17.46–59.77%) | H1 | NEUROD | Puromycin KI KI | [117] | ||
ABT | 6.8-fold (7.86–53.50%) | DiPSC | NEUROD | Puromycin KI | [117] | |
4.6-fold (17.46–79.91%) | H1 | NEUROD | Puromycin KI | [117] | ||
RO-3306 | 1.3-fold(18.1–23.5%) | PBSC | β-globin | GC | [118] | |
Golgi apparatus | Brefeldin A | 2-fold (17.7%–27.2%) | E14 mouse ESCs | Nanog | GFP KI | [112] |
inhibitor | 1.3-fold (13%–17%) | iPSC | CTNB1 | KI | [131] | |
β3-adrenergic receptor agonist | L755507 | 3-fold (17.7–33.3%) | E14 mouse ESCs | Nanog | GFP KI | [112] |
8.9-fold (0.35–3.13%) | iPSC | SOD1 | A4V GC | [112] | ||
2-fold (0.8–1.6%) | HUVEC | ACTA2 | Venus KI | [112] | ||
1.9-fold (5.6–10.9%) | Porcine fetal fibroblasts | eGFP | GC | [86] | ||
NS | iPSC | CTNB1/PRDM14 | mNeoGreen KI | [97] |
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Yang, H.; Ren, S.; Yu, S.; Pan, H.; Li, T.; Ge, S.; Zhang, J.; Xia, N. Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks. Int. J. Mol. Sci. 2020, 21, 6461. https://doi.org/10.3390/ijms21186461
Yang H, Ren S, Yu S, Pan H, Li T, Ge S, Zhang J, Xia N. Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks. International Journal of Molecular Sciences. 2020; 21(18):6461. https://doi.org/10.3390/ijms21186461
Chicago/Turabian StyleYang, Han, Shuling Ren, Siyuan Yu, Haifeng Pan, Tingdong Li, Shengxiang Ge, Jun Zhang, and Ningshao Xia. 2020. "Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks" International Journal of Molecular Sciences 21, no. 18: 6461. https://doi.org/10.3390/ijms21186461