دورية أكاديمية
MORC2 signaling integrates phosphorylation-dependent, ATPase-coupled chromatin remodeling during the DNA damage response
العنوان: | MORC2 signaling integrates phosphorylation-dependent, ATPase-coupled chromatin remodeling during the DNA damage response |
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المؤلفون: | Li, Da-Qiang, Nair, Sujit S., Ohshiro, Kazufumi, Kumar, Anupam, Nair, Vasudha S., Pakala, Suresh B., Reddy, Sirigiri Divijendra Natha, Gajula, Rajendra P., Eswaran, Jeyanthy, Aravind, L., Kumar, Rakesh |
المصدر: | Biochemistry and Molecular Medicine Faculty Publications |
بيانات النشر: | Health Sciences Research Commons |
سنة النشر: | 2012 |
المجموعة: | George Washington University: Health Sciences Research Commons (HSRC) |
مصطلحات موضوعية: | Adenosine Triphosphatases--metabolism, Chromatin Assembly and Disassembly, DNA Damage, Transcription Factors--metabolism, Biochemistry, Biophysics, and Structural Biology |
الوصف: | Chromatin dynamics play a central role in maintaining genome integrity, but how this is achieved remains largely unknown. Here, we report that microrchidia CW-type zinc finger 2 (MORC2), an uncharacterized protein with a derived PHD finger domain and a conserved GHKL-type ATPase module, is a physiological substrate of p21-activated kinase 1 (PAK1), an important integrator of extracellular signals and nuclear processes. Following DNA damage, MORC2 is phosphorylated on serine 739 in a PAK1-dependent manner, and phosphorylated MORC2 regulates its DNA-dependent ATPase activity to facilitate chromatin remodeling. Moreover, MORC2 associates with chromatin and promotes gamma-H2AX induction in a PAK1 phosphorylation-dependent manner. Consequently, cells expressing MORC2-S739A mutation displayed a reduction in DNA repair efficiency and were hypersensitive to DNA-damaging agent. These findings suggest that the PAK1-MORC2 axis is critical for orchestrating the interplay between chromatin dynamics and the maintenance of genomic integrity through sequentially integrating multiple essential enzymatic processes. |
نوع الوثيقة: | text |
وصف الملف: | application/pdf |
اللغة: | unknown |
العلاقة: | https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/28Test; https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=1027&context=smhs_biochem_facpubsTest |
الإتاحة: | https://hsrc.himmelfarb.gwu.edu/smhs_biochem_facpubs/28Test https://hsrc.himmelfarb.gwu.edu/cgi/viewcontent.cgi?article=1027&context=smhs_biochem_facpubsTest |
حقوق: | http://creativecommons.org/licenses/by-nc-nd/3.0Test/ |
رقم الانضمام: | edsbas.101A5C86 |
قاعدة البيانات: | BASE |
الوصف غير متاح. |