Genetics. Published Articles Ahead of Print: May 27, 2008, Copyright © 2008
doi:10.1534/genetics.107.085779


A more recent version of this article appeared on June 1, 2008.

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S. pombe histone acetyltransferase Mst1 (KAT5) is an essential protein required for damage response and chromosome segregation

Eliana Gómez 1, Rebecca Nugent 1, Sebastian Laria 2 and Susan L. Forsburg 1*

1 University of Southern California
2 The Salk Institute

* To whom correspondence should be addressed. E-mail: forsburg{at}usc.edu.

Submitted on December 12, 2007
Revised on January 18, 2008
Accepted on 4 April 2008


Abstract

S. pombe Mst1 is a member of the MYST family of histone acetyltransferases, and is the likely ortholog of S. 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.

Key Words: HAT, Swi6, chromatin, damage, fission yeast