ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells
| Autor: | Junchao Dong, Rafael Casellas, Qiu Wu, Xiaoqi Zheng, Wubing Zhang, Pengfei Dai, Tengfei Xiao, Xiaojing Liu, Dingpeng Yang, Jiazhi Hu, Shan Zha, Brian J. Lee, X. Shirley Liu, Min Huang, Leng-Siew Yeap, Tingting Liu, Bo O. Zhou, Yafang Shang, Liu Daisy Liu, Fei-Long Meng |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
DNA End-Joining Repair
DNA repair Molecular biology Immunology Double-strand DNA breaks Biology Article law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law CRISPR Humans Animals Gene Regulatory Networks 030304 developmental biology Mammals Mice Knockout 0303 health sciences B-Lymphocytes DNA Helicases Cell Biology DNA Research Highlight Immunoglobulin Class Switching V(D)J Recombination Chromatin Cell biology DNA-Binding Proteins HEK293 Cells chemistry Immunoglobulin class switching Immunoglobulin G Mutation Recombinant DNA CRISPR-Cas Systems 030217 neurology & neurosurgery Recombination DNA Damage Protein Binding |
| Zdroj: | Cell Research |
| ISSN: | 1748-7838 1001-0602 |
| Popis: | Programmed DNA recombination in mammalian cells occurs predominantly in a directional manner. While random DNA breaks are typically repaired both by deletion and by inversion at approximately equal proportions, V(D)J and class switch recombination (CSR) of immunoglobulin heavy chain gene overwhelmingly delete intervening sequences to yield productive rearrangement. What factors channel chromatin breaks to deletional CSR in lymphocytes is unknown. Integrating CRISPR knockout and chemical perturbation screening we here identify the Snf2-family helicase-like ERCC6L2 as one such factor. We show that ERCC6L2 promotes double-strand break end-joining and facilitates optimal CSR in mice. At the cellular levels, ERCC6L2 rapidly engages in DNA repair through its C-terminal domains. Mechanistically, ERCC6L2 interacts with other end-joining factors and plays a functionally redundant role with the XLF end-joining factor in V(D)J recombination. Strikingly, ERCC6L2 controls orientation-specific joining of broken ends during CSR, which relies on its helicase activity. Thus, ERCC6L2 facilitates programmed recombination through directional repair of distant breaks. |
| Databáze: | OpenAIRE |
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