MCB Accepts, published online ahead of print on 19 February 2008

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jha, S. Articles by Dutta, A. Search for Related Content PubMed PubMed Citation Articles by Jha, S. Articles by Dutta, A.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.01983-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Human Rvb1/Tip49 is required for the HAT activity of TIP60/NuA4 and for the downregulation of phosphorylation on H2AX after DNA damage

Sudhakar Jha, Etsuko Shibata, and Anindya Dutta^*

Department of Biochemistry and Molecular Genetics, University of Virginia, School of Medicine, Jordan 1240, 1300 Jefferson Park Ave, Charlottesville, VA 22908, USA

^* To whom correspondence should be addressed. Email: ad8q{at}virginia.edu.

The role of chromatin-remodeling factors in transcription is well established but the link between chromatin-remodeling complexes and DNA repair remains unexplored. Human Rvb1/Rvb2 are highly conserved AAA+ ATP binding proteins that are part of various chromatin-remodeling complexes such as Ino80, SRCAP and Tip60/NuA4, but their molecular function is unclear. Depletion of Rvb1 increases the amount and persistence of phosphorylation on chromatin-associated H2AX after exposure of cells to UV irradiation, or to mitomycin C, cisplatin, camptothecin or etoposide, without increasing the amount of DNA damage. Tip60 depletion, but not Ino80 or SRCAP depletion, mimics the effect of Rvb1 depletion on H2AX phosphorylation. Rvb1 is required for the histone H4 acetyl transferase activity of the Tip60 complex and histone H4 acetylation is required prior to the dephosphorylation of phosphoH2AX. Thus Rvb1 is critical for the dephosphorylation of phosphoH2AX due to its role in maintaining the HAT activity of Tip60/NuA4, implicating the Rvb1-Tip60 complex in the chromatin-remodeling response of cells after DNA damage.

This article has been cited by other articles:

• McKeegan, K. S., Debieux, C. M., Watkins, N. J. (2009). Evidence that the AAA+ Proteins TIP48 and TIP49 Bridge Interactions between 15.5K and the Related NOP56 and NOP58 Proteins during Box C/D snoRNP Biogenesis. Mol. Cell. Biol. 29: 4971-4981 [Abstract] [Full Text]  
• Reynard, L. N., Cocquet, J., Burgoyne, P. S. (2009). The Multi-Copy Mouse Gene Sycp3-Like Y-Linked (Sly) Encodes an Abundant Spermatid Protein That Interacts with a Histone Acetyltransferase and an Acrosomal Protein. Biol. Reprod. 81: 250-257 [Abstract] [Full Text]  
• Kinner, A., Wu, W., Staudt, C., Iliakis, G. (2008). {gamma}-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res 36: 5678-5694 [Abstract] [Full Text]  
• Huber, O., Menard, L., Haurie, V., Nicou, A., Taras, D., Rosenbaum, J. (2008). Pontin and Reptin, Two Related ATPases with Multiple Roles in Cancer. Cancer Res. 68: 6873-6876 [Abstract] [Full Text]