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

Abstract

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 temperaturesensitive 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.

Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin boundaries

“…We found that a mst1-1 allele, which contains a temperature-sensitive L344S mutation (Gomez et al 2008), resulted in heterochromatin spreading past IRC1R even at a permissive temperature, as indicated by the silencing of IRC1RTura4…”

“…Among the histone acetyltransferases (HATs) in fission yeast, Mst1 is a member of the highly conserved MYST family of HATs, and it forms a complex similar to the NuA4 complex of budding yeast (Gomez et al , 2008Shevchenko et al 2008), which acetylates H4K16 (Lee and Workman 2007). We found that a mst1-1 allele, which contains a temperature-sensitive L344S mutation (Gomez et al 2008), resulted in heterochromatin spreading past IRC1R even at a permissive temperature, as indicated by the silencing of IRC1RTura4…”

“…We discovered that the fission yeast MYST family acetyltransferase Mst1 is required for H4K16ac and the binding of Bdf2 at IRCs, and a mutation in Mst1 also resulted in defects in boundary formation at IRCs. Mst1 forms a complex with composition similar to that of the budding yeast NuA4, which acetylates H4K16 as well as other residues (Lee and Workman 2007;Gomez et al 2008;Shevchenko et al 2008). However, in budding yeast, mutations in Esa1, the catalytic subunit of NuA4, have no effect on telomeric heterochromatin assembly (Kimura et al 2002;Suka et al 2002).…”

A chromodomain switch mediated by histone H3 Lys 4 acetylation regulates heterochromatin assembly

“…However, this initial collection did not contain Mst1, because this HAT is an essential protein. Therefore, we obtained a previously described thermosensitive (ts) mutant of mst1 (Gomez et al 2008). IF analysis revealed that the nuclear signal obtained with the anti-H3K4ac antibody was greatly reduced when the mst1-ts mutant was switched to the nonpermissive temperature even for a very short period of time (2 h) (Fig.…”

Nitrogen depletion in the fission yeast Schizosaccharomyces pombe causes nucleosome loss in both promoters and coding regions of activated genes

“…Moreover, the urg1 + gene was still induced in a strain lacking the mst2 + gene and at the restrictive temperature in a strain with a ts mutation in the mst1 + gene (Gomez et al 2008), indicating that the two HATs of the MYST subfamily that are encoded by these genes are not responsible (at least not alone) for the increase in histone acetylation during gene activation by nitrogen depletion (data not shown). In summary, there was a pronounced nucleosome loss throughout the strongly induced urg1 + gene in response to nitrogen depletion, but the lack of effects of all mutations tested so far suggests that this loss was likely dependent on several redundant nucleosome remodelers and/or other mechanisms that remain to be identified.…”