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

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 restr...

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Bibliographic Details
Published in:Genetics (Austin) 2008-06, Vol.179 (2), p.757-771
Main Authors: Gomez, Eliana B, Nugent, Rebecca L, Laria, Sebastian, Forsburg, Susan L
Format: Article
Language:English
Subjects:
acyltransferases
Alleles
Base Sequence
chromosome segregation
Chromosomes, Fungal - genetics
DNA damage
DNA Damage - genetics
DNA methyltransferase
DNA Primers - genetics
DNA repair
DNA Repair - genetics
DNA Replication - genetics
DNA, Fungal - genetics
DNA-binding proteins
Genes, Fungal
Genetics
Genomic Instability
Heterochromatin - genetics
histone acetyltransferase
Histone Acetyltransferases - metabolism
Hydroxyurea - pharmacology
Investigations
Kinases
methyltransferases
Mitosis - genetics
Mutation
Phenotype
protein-protein interactions
Proteins
Recombination, Genetic
Schizosaccharomyces - cytology
Schizosaccharomyces - drug effects
Schizosaccharomyces - enzymology
Schizosaccharomyces - genetics
Schizosaccharomyces pombe
Temperature
Two-Hybrid System Techniques
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Summary: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.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1534/genetics.107.085779