| Autor: |
Susan B. Olson, Tailai Chen, Eunju Kang, Amy Koski, Jianhui Gong, Jingye Zhang, Crystal Van Dyken, Chong-Jai Kim, P. Barton Duell, Han Zhao, Sanjiv Kaul, Ying Gu, Stephen B. Heitner, Sacha A. Krieg, Yeon-Mi Lee, Ying Li, Sang-Wook Park, Jumi Park, Zi-Jiang Chen, Thanasup Gonmanee, Hong Ma, Riffat Ahmed, Keliang Wu, Hui Yang, Tomonari Hayama, Jin-Soo Kim, Yue Shen, David Battaglia, Dan Liang, Hayley Darby, Paula Amato, Zhenzhen Hou, Aleksei Mikhalchenko, Thomas O'Leary, David M. Lee, Diana H. Wu, Yilin Yuan, Shoukhrat Mitalipov, Nuria Marti Gutierrez |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.06.19.162214 |
| Popis: |
Applications of genome editing ultimately depend on DNA repair triggered by targeted double-strand breaks (DSBs). However, repair mechanisms in human cells remain poorly understood and vary across different cell types. Here we report that DSBs selectively induced on a mutant allele in heterozygous human embryos are repaired by gene conversion using an intact wildtype homolog as a template in up to 40% of targeted embryos. We also show that targeting of homozygous loci facilitates an interplay of non-homologous end joining (NHEJ) and gene conversion and results in embryos which carry identical indel mutations on both loci. Additionally, conversion tracks may expand bidirectionally well beyond the target region leading to an extensive loss of heterozygosity (LOH). Our study demonstrates that gene conversion and NHEJ are two major DNA DSB repair mechanisms in preimplantation human embryos. While gene conversion could be applicable for gene correction, extensive LOH presents a serious safety concern. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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