The role of MutY homolog (Myh1) in controlling the histone deacetylase Hst4 in the fission yeast Schizosaccharomyces pombe.
The DNA glycosylase MutY homolog (Myh1) excises adenines misincorporated opposite guanines or 7,8-dihydro-8-oxo-guanines on DNA by base excision repair thereby preventing G:C to T:A mutations. Schizosaccharomyces pombe (Sp) Hst4 is an NAD(+)-dependent histone/protein deacetylase involved in gene silencing and maintaining genomic integrity. Hst4 regulates deacetylation of histone 3 Lys56 at the entry and exit points of the nucleosome core particle. Here, we demonstrate that the hst4 mutant is more sensitive to H(2)O(2) than wild-type cells. H(2)O(2) treatment results in an SpMyh1-dependent decrease in SpHst4 protein level and hyperacetylation of histone 3 Lys56. Furthermore, SpHst4 interacts with SpMyh1 and the cell cycle checkpoint Rad9-Rad1-Hus1 (9-1-1) complex. SpHst4, SpMyh1, and SpHus1 are physically bound to telomeres. Following oxidative stress, there is an increase in the telomeric association of SpMyh1. Conversely, the telomeric association of spHst4 is decreased. Deletion of SpMyh1 strongly abrogated telomeric association of SpHst4 and SpHus1. However, telomeric association of SpMyh1 is enhanced in hst4Δ cells in the presence of chronic DNA damage. These results suggest that SpMyh1 repair regulates the functions of SpHst4 and the 9-1-1 complex in maintaining genomic stability.
Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, 108 North Greene Street, Baltimore, MD 21201, USA.
Dau-Yin
DY
Chang
Guoli
G
Shi
Mickaël
M
Durand-Dubief
Karl
K
Ekwall
A-Lien
AL
Lu
D000107:Acetylation; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; C106332:hus1 protein, S pombe; C069930:rad9 protein; D006861:Hydrogen Peroxide; D004720:Endonucleases; C499354:rad1 protein, S pombe; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; C530050:Hst4 protein, S pombe; D006655:Histone Deacetylases