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


CONCLUSIONS
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.
Suter
Bernhard
B
Program in Proteomics and Bioinformatics, Banting and Best Department of Medical Genetics, University of Toronto, Toronto, Ontario, Canada. bernhard.suter@utoronto.ca
Pogoutse
Oxana
O
Guo
Xinghua
X
Krogan
Nevan
N
Lewis
Peter
P
Greenblatt
Jack F
JF
Rine
Jasper
J
Emili
Andrew
A
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D051548:Histone Acetyltransferases; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D009154:Mutation; D016366:Open Reading Frames; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D004271:DNA, Fungal; D006657:Histones; D051738:Origin Recognition Complex; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex; D008239:Lysine