HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 2, 836-842, January 12, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/2/836    most recent M607464200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Benson, L. J. Articles by Annunziato, A. T. Search for Related Content PubMed PubMed Citation Articles by Benson, L. J. Articles by Annunziato, A. T. Social Bookmarking                      What's this?

Properties of the Type B Histone Acetyltransferase Hat1

H4 TAIL INTERACTION, SITE PREFERENCE, AND INVOLVEMENT IN DNA REPAIR^*

Laura J. Benson, Jane A. Phillips¹, Yongli Gu, Mark R. Parthun, Charles S. Hoffman, and Anthony T. Annunziato²

From the Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467 and Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, Ohio State University, Columbus, Ohio 43210

The Hat1 histone acetyltransferase catalyzes the acetylation of H4 at lysines 5 and 12, the same sites that are acetylated in newly synthesized histone H4. By performing histone acetyltransferase (HAT) assays on various synthetic H4 N-terminal peptides, we have examined the interactions between Hat1 and the H4 tail domain. It was found that acetylation requires the presence of positively charged amino acids at positions 8 and 16 of H4, positions that are normally occupied by lysine; however, lysine per se is not essential and can be replaced by arginine. In contrast, replacing Lys-8 and -16 of H4 with glutamines reduces acetylation to background levels. Similarly, phosphorylation of Ser-1 of the H4 tail depresses acetylation by both yeast Hat1p and the human HAT-B complex. These results strongly support the model proposed by Ramakrishnan and colleagues for the interaction between Hat1 and the H4 tail (Dutnall, R. N., Tafrov, S. T., Sternglanz, R., and Ramakrishnan, V. (1998) Cell 94, 427–438) and may have implications for the genetic analysis of histone acetylation. It was also found that Lys-12 of H4 is preferentially acetylated by human HAT-B, in further agreement with the proposed model of H4 tail binding. Finally, we have demonstrated that deletion of the hat1 gene from the fission yeast Schizosaccharomyces pombe causes increased sensitivity to the DNA-damaging agent methyl methanesulfonate in the absence of any additional mutations. This is in contrast to results obtained with a Saccharomyces cerevisiae hat1 strain, which must also carry mutations of the acetylatable lysines of H3 for heightened methyl methanesulfonate sensitivity to be observed. Thus, although the role of Hat1 in DNA damage repair is evolutionarily conserved, the ability of H3 acetylation to compensate for Hat1 deletion appears to be more variable.

Received for publication, August 7, 2006 , and in revised form, October 18, 2006.

^* This work was supported by NIGMS, National Institutes of Health Grants GM46226 (to C. S. H.), GM62970 (to M. R. P.), and GM35837 (to A. T. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ Current address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.

² To whom correspondence should be addressed: Dept. of Biology, Boston College, 140 Commonwealth Ave., Chestnut Hill, MA 02467. Tel.: 617-552-3812; Fax: 617-552-2011; E-mail: annunzia{at}bc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. L. Mersfelder and M. R. Parthun Involvement of Hat1p (Kat1p) Catalytic Activity and Subcellular Localization in Telomeric Silencing J. Biol. Chem., October 24, 2008; 283(43): 29060 - 29068. [Abstract] [Full Text] [PDF]