Academic Journal
Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations
| العنوان: | Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations |
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| المؤلفون: | Jiying Sun, Lin Shi, Aiko Kinomura, Atsuhiko Fukuto, Yasunori Horikoshi, Yukako Oma, Masahiko Harata, Masae Ikura, Tsuyoshi Ikura, Roland Kanaar, Satoshi Tashiro |
| المصدر: | eLife, Vol 7 (2018) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | ATM, ARP8 phosphorylation, chromosome translocations, INO80, RAD51, ATR, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment. The etoposide-induced phosphorylation of ARP8 is regulated by ATM and ATR, and attenuates its interaction with INO80. The ATM-regulated phosphorylation of ARP8 reduces the excessive loading of INO80 and RAD51 onto the breakpoint cluster region. These findings suggest that the phosphorylation of ARP8, regulated by ATM, plays an important role in maintaining the fidelity of DNA repair to prevent the etoposide-induced 11q23 abnormalities. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/32222; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.32222 |
| URL الوصول: | https://doaj.org/article/7d76dfc60db74112bd8e5db6c97f123b |
| رقم الانضمام: | edsdoj.7d76dfc60db74112bd8e5db6c97f123b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.32222 |