Originally published as Genetics Published Articles Ahead of Print on May 27, 2008.

Genetics, Vol. 179, 757-771, June 2008, Copyright © 2008
doi:10.1534/genetics.107.085779

Schizosaccharomyces pombe Histone Acetyltransferase Mst1 (KAT5) Is an Essential Protein Required for Damage Response and Chromosome Segregation

Eliana B. Gómez*,{dagger}, Rebecca L. Nugent*, Sebastián Laria{dagger} and Susan L. Forsburg*,{dagger},1

* Molecular and Computational Biology Section, University of Southern California, Los Angeles, California 90089-2910 and {dagger} Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 90089-2910

1 Corresponding author: Molecular and Computational Biology Section, 1050 Childs Way, RRI 201, University of Southern California, Los Angeles, CA 90089-2910.
E-mail: forsburg{at}usc.edu

Schizosaccharomyces pombe Mst1 is a member of the MYST family of histone acetyltransferases and is the likely ortholog of Saccharomyces cerevisiae Esa1 and human Tip60 (KAT5). We have isolated a temperature-sensitive allele of this essential gene. mst1 cells show a pleiotropic phenotype at the restrictive temperature. They are sensitive to a variety of DNA-damaging agents and to the spindle poison thiabendazole. mst1 has an increased frequency of Rad22 repair foci, suggesting endogenous damage. Two-hybrid results show that Mst1 interacts with a number of proteins involved in chromosome integrity and centromere function, including the methyltransferase Skb1, the recombination mediator Rad22 (Sc Rad52), the chromatin assembly factor Hip1 (Sc Hir1), and the Msc1 protein related to a family of histone demethylases. mst1 mutant sensitivity to hydroxyurea suggests a defect in recovery following HU arrest. We conclude that Mst1 plays essential roles in maintenance of genome stability and recovery from DNA damage.