MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response
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 physiol...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712004159 |
| _version_ | 1818056366299807744 |
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| author | Da-Qiang Li Sujit S. Nair Kazufumi Ohshiro Anupam Kumar Vasudha S. Nair Suresh B. Pakala Sirigiri Divijendra Natha Reddy Rajendra P. Gajula Jeyanthy Eswaran L. Aravind Rakesh Kumar |
| author_facet | Da-Qiang Li Sujit S. Nair Kazufumi Ohshiro Anupam Kumar Vasudha S. Nair Suresh B. Pakala Sirigiri Divijendra Natha Reddy Rajendra P. Gajula Jeyanthy Eswaran L. Aravind Rakesh Kumar |
| author_sort | Da-Qiang Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T12:27:42Z |
| format | Article |
| id | doaj.art-4a763e2521174a0f8577823efa540073 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T12:27:42Z |
| publishDate | 2012-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4a763e2521174a0f8577823efa5400732022-12-22T01:48:54ZengElsevierCell Reports2211-12472012-12-01261657166910.1016/j.celrep.2012.11.018MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage ResponseDa-Qiang Li0Sujit S. Nair1Kazufumi Ohshiro2Anupam Kumar3Vasudha S. Nair4Suresh B. Pakala5Sirigiri Divijendra Natha Reddy6Rajendra P. Gajula7Jeyanthy Eswaran8L. Aravind9Rakesh Kumar10Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USANational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USADepartment of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USAChromatin 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.http://www.sciencedirect.com/science/article/pii/S2211124712004159 |
| spellingShingle | Da-Qiang Li Sujit S. Nair Kazufumi Ohshiro Anupam Kumar Vasudha S. Nair Suresh B. Pakala Sirigiri Divijendra Natha Reddy Rajendra P. Gajula Jeyanthy Eswaran L. Aravind Rakesh Kumar MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response Cell Reports |
| title | MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response |
| title_full | MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response |
| title_fullStr | MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response |
| title_full_unstemmed | MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response |
| title_short | MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response |
| title_sort | morc2 signaling integrates phosphorylation dependent atpase coupled chromatin remodeling during the dna damage response |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712004159 |
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