ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells
| العنوان: | ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells |
|---|---|
| المؤلفون: | 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 |
| المصدر: | Cell Research |
| بيانات النشر: | Springer Singapore, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1748-7838 1001-0602 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9edb9a2abd1e09a4aa0790c0a788a69bTest http://europepmc.org/articles/PMC7608219Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9edb9a2abd1e09a4aa0790c0a788a69b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17487838 10010602 |
|---|