Research article

Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

Bernhard Suter^1,2 , Oxana Pogoutse¹ , Xinghua Guo¹ , Nevan Krogan^1,3 , Peter Lewis⁴ , Jack F Greenblatt¹ , Jasper Rine² and Andrew Emili¹

¹Program in Proteomics and Bioinformatics, Banting and Best Department of Medical Genetics, Department of Medical and Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

²Department of Molecular & Cell Biology, University of California, Berkeley, CA, USA

³Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA

⁴Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

author email corresponding author email

BMC Biology 2007, 5:38doi:10.1186/1741-7007-5-38

Published:	19 September 2007

Abstract

Background

Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4.

Results

Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC). While mutational inactivation of the histone acetyltransferase (HAT) gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2) exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork.

Conclusion

We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p). The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.