The Role of MutY Homolog (Myh1) in Controlling the Histone Deacetylase Hst4 in the Fission Yeast Schizosaccharomyces pombe

JOURNAL OF MOLECULAR BIOLOGY

卷:405

Article

Chang, Dau-Yin¹  Shi, Guoli¹  Durand-Dubief, Mickael²  Ekwall, Karl²  Lu, A-Lien¹ 

[1] Univ Maryland, Dept Biochem & Mol Biol, Sch Med, Baltimore, MD 21201 USA

[2] Karolinska Inst, Novum, Dept Biosci & Nutr, Ctr Biosci, S-14157 Huddinge, Sweden

关键词: DNA glycosylase;    MYH;    Hst4;    histone deacetylase;    DNA repair;   

DOI  :  10.1016/j.jmb.2010.11.037

来源: Elsevier

【 摘 要 】

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 H2O2 than wild-type cells. H2O2 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 hst4 Delta 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. (C) 2010 Elsevier Ltd. All rights reserved.

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