MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response

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

doi:10.1016/j.celrep.2012.11.018

Cell Reports (Dec 2012)

MORC2 Signaling Integrates Phosphorylation-Dependent, ATPase-Coupled Chromatin Remodeling during the DNA Damage Response

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

Affiliations

Da-Qiang Li: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Sujit S. Nair: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Kazufumi Ohshiro: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Anupam Kumar: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Vasudha S. Nair: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Suresh B. Pakala: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Sirigiri Divijendra Natha Reddy: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Rajendra P. Gajula: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
Jeyanthy Eswaran: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA
L. Aravind: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
Rakesh Kumar: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC 20037, USA

DOI: https://doi.org/10.1016/j.celrep.2012.11.018
Journal volume & issue: Vol. 2, no. 6
pp. 1657 – 1669

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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