WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity Journal Article
| Authors: | Xiao, A.; Li, H.; Shechter, D.; Ahn, S. H.; Fabrizio, L. A.; Erdjument-Bromage, H.; Ishibe-Murakami, S.; Wang, B.; Tempst, P.; Hofmann, K.; Patel, D. J.; Elledge, S. J.; Allis, C. D. |
| Article Title: | WSTF regulates the H2A.X DNA damage response via a novel tyrosine kinase activity |
| Abstract: | DNA double-stranded breaks present a serious challenge for eukaryotic cells. The inability to repair breaks leads to genomic instability, carcinogenesis and cell death. During the double-strand break response, mammalian chromatin undergoes reorganization demarcated by H2A.X Ser 139 phosphorylation (γ-H2A.X). However, the regulation of γ-H2A.X phosphorylation and its precise role in chromatin remodelling during the repair process remain unclear. Here we report a new regulatory mechanism mediated by WSTF (Williams-Beuren syndrome transcription factor, also known as BAZ1B) - a component of the WICH complex (WSTF-ISWI ATP-dependent chromatin-remodelling complex). We show that WSTF has intrinsic tyrosine kinase activity by means of a domain that shares no sequence homology to any known kinase fold. We show that WSTF phosphorylates Tyr 142 of H2A.X, and that WSTF activity has an important role in regulating several events that are critical for the DNA damage response. Our work demonstrates a new mechanism that regulates the DNA damage response and expands our knowledge of domains that contain intrinsic tyrosine kinase activity. ©2009 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | controlled study; protein phosphorylation; unclassified drug; nonhuman; protein domain; animal cell; mouse; mammalia; animals; chromosomal proteins, non-histone; mice; dna damage; animal experiment; transcription factor; enzyme activity; protein tyrosine kinase; tyrosine; phosphorylation; transcription factors; dna; regulatory mechanism; eukaryota; amino acid; protein structure, tertiary; protein-tyrosine kinases; sequence homology; histones; adenosine triphosphatases; nih 3t3 cells; chromatin assembly and disassembly; nucleosomes; williams beuren syndrome trasncription factor; damage; phosphotyrosine |
| Journal Title: | Nature |
| Volume: | 457 |
| Issue: | 7225 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-01-01 |
| Start Page: | 57 |
| End Page: | 62 |
| Language: | English |
| DOI: | 10.1038/nature07668 |
| PUBMED: | 19092802 |
| PROVIDER: | scopus |
| PMCID: | PMC2854499 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 39" - "Export Date: 30 November 2010" - "CODEN: NATUA" - "Source: Scopus" |
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