C1orf109L binding DHX9 promotes DNA damage depended on the R-loop accumulation and enhances camptothecin chemosensitivity
| العنوان: | C1orf109L binding DHX9 promotes DNA damage depended on the R-loop accumulation and enhances camptothecin chemosensitivity |
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| المؤلفون: | Yiqun Li, Haoxiu Sun, Dandan Zhang, Xiaohan Zhang, Shupei Qiao, Xiaoqing Zhang, Yanpeng Ci, Fang Han, Wanqiu Xie, Peng Dou, Huan Nie, Yu Li |
| المصدر: | Cell Proliferation |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell cycle checkpoint, DNA damage, Immunoprecipitation, chemotherapy, DEAD-box RNA Helicases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, PARP1, Transcription (biology), Neoplasms, medicine, Humans, R‐loop‐associated proteins, G2/M phase arrest, R‐loop, Chemistry, Cell Biology, General Medicine, Cell Cycle Checkpoints, Original Articles, Cell cycle, Phosphoproteins, Antineoplastic Agents, Phytogenic, Cell biology, Neoplasm Proteins, 030104 developmental biology, HEK293 Cells, 030220 oncology & carcinogenesis, C1orf109L, Camptothecin, Original Article, R-Loop Structures, DNA, medicine.drug, HeLa Cells, Protein Binding |
| الوصف: | Objectives R‐loop is a three‐stranded nucleic acid structure of RNA/DNA hybrid, which occurs naturally during transcription, and more R‐loop accumulation can trigger serious DNA damage. There has been increasing attention to the issue of R‐loop accumulation acted as a target for cancer therapy. However, the regulation of R‐loop‐associated proteins is poorly explored. Material and method Quantitative real‐time PCR and Western blot were used to measure the expression of C1orf109 in cell lines. In addition, C1orf109L (C1orf109 longest isoform) protein binding partner was identified and validated using immunoprecipitation‐mass spectrometric (IP‐MS) and immunoprecipitation assays. DNA‐RNA immunoprecipitation (DR‐IP) and immunofluorescence determined the C1orf109L location on R‐loop. R‐loop accumulation was determined by immunofluorescence. Cell cycle was determined by flow cytometry. Finally, time‐lapse assay and cell counting were conducted to determined cell survival in response to camptothecin (CPT). Results We found that C1orf109L could mediate cell cycle arrest in the G2/M phase and DNA damage depended on R‐loop accumulation. Meanwhile, C1orf109L could bind with DHX9 to trigger R‐loop accumulation. And C1orf109L was competitive with PARP1 binding to DHX9, which would block the function of DHX9‐PARP1 to prevent the R‐loop accumulation. Furthermore, C1orf109L could enhance the chemosensitivity of CPT, a chemotherapeutic drug capable of promoting R‐loop formation. Conclusions Our data demonstrate that C1orf109L triggers R‐loop accumulation and DNA damage to arrest cell cycle. C1orf109L could compete with PARP1 for DHX9 binding, which mediates DNA damage and cell cycle arrest via triggering R‐loop accumulation. Furthermore, C1orf109L could enhance the chemosensitivity of camptothecin, a chemotherapeutic drug capable of promoting R‐loop formation. |
| تدمد: | 1365-2184 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52304081699e61e4a740d7cbb6651460 https://pubmed.ncbi.nlm.nih.gov/32761833 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....52304081699e61e4a740d7cbb6651460 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652184 |
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