Boisvert, François-Michel, Rhie, Alexandre, Richard, Stéphane and Doherty, Aidan J (2005) The GAR motif of 53BP1 is a target for PRMT1 methylation and directs chromatin localisation in response to DNA damage. Cell Cycle, 4 (12). pp. 1834-1841. ISSN 1538-4101

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Abstract

The p53-binding protein 1 (53BP1) is rapidly recruited to sites of DNA double-strand breaks and forms characteristics nuclear foci, demonstrating its role in the early events of detection, signaling and repair of damaged DNA. 53BP1 contains a glycine arginine rich (GAR) motif of unknown function within its kinetochore binding domain. Herein, we show that the GAR motif of 53BP1 is arginine methylated by protein arginine methyltransferase 1 (PRMT1), the same methyltransferase that methylates MRE11. 53BP1 contains asymmetric dimethylarginines (aDMA) within cells, as detected with methylarginine-specific antibodies. Amino acid substitution of the arginines within the GAR motif of 53BP1 abrogated binding to single and double-stranded DNA, demonstrating that the GAR motif is required for DNA binding activity of 53BP1. Fibroblast cells treated with methylase inhibitors failed to relocalize 53BP1 to sites of DNA damage and formed few ?-H2AX foci, consistent with our previous data that MRE11 fails to relocalize to DNA damage sites in cells treated with methylase inhibitors. Our findings identify the GAR motif as a region required for 53BP1 DNA binding activity and is the site of methylation by PRMT1.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User:	Aidan Doherty
Date Deposited:	06 Feb 2012 21:08
Last Modified:	03 Apr 2012 09:45
URI:	http://sro.sussex.ac.uk/id/eprint/29761

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