Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent

Krishnan, N., Jeong, D. G., Jung, S.-k., Ryu, S. E., Xiao, A., Allis, C. D., Kim, S. J., Tonks, N. K. (2009) Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent. Journal of Biological Chemistry, 284 (24). pp. 16066-16070.

URL: http://www.ncbi.nlm.nih.gov/pubmed/19351884
DOI: 10.1074/jbc.C900032200

Abstract

In mammalian cells, the DNA damage-related histone H2A variant H2A.X is characterized by a C-terminal tyrosyl residue, Tyr-142, that is phosphorylated by an atypical kinase, WSTF. The phosphorylation status of Tyr-142 in H2A.X has been shown to be an important regulator of the DNA damage response by controlling the formation of �H2A.X foci, which are platforms for recruiting molecules involved in DNA damage repair and signaling. In this manuscript, we present evidence to support the identification of the Eyes Absent (EYA) phosphatases, protein tyrosine phosphatases of the haloacid dehalogenase superfamily, as being capable of dephosphorylating the C-terminal tyrosyl residue of histone H2A.X. We demonstrate that EYA2 and EYA3 displayed specificity for Tyr-142 of H2A.X in assays in vitro. Suppression of eya3 by RNA interference resulted in elevated basal phosphorylation, and inhibited DNA damage-induced dephosphorylation, of Tyr-142 of H2A.X in vivo. The study provides the first indication of a physiological substrate for the EYA phosphatases and suggests a novel role for these enzymes in the regulation of the DNA damage response.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein phosphatase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Animal Services
CSHL labs > Tonks lab
Depositing User: Matt Covey
Date Deposited: 21 Feb 2013 17:21
Last Modified: 29 Dec 2014 17:53
PMCID: PMC2713548
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27357

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