title: Anaphase-promoting complex/cyclosome-mediated proteolysis of Ams2 in the G1 phase ensures the coupling of histone gene expression to DNA replication in fission yeast.
abstract: Histone transcription and deposition are tightly regulated with the DNA replication cycle to maintain genetic integrity. Ams2 is a GATA-containing transcription factor responsible for core histone gene expression and for CENP-A loading at centromeres in fission yeast. Ams2 levels are cell cycle-regulated, and after the S phase Ams2 is degraded by the SCF(pof3) ubiquitin ligase; however, the regulation of Ams2 in G(1) or meiosis is poorly understood. Here we show that another ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C) targets Ams2 for destruction in G(1). Ubiquitylation and destruction of Ams2 is dependent upon a coactivator Cdh1/Ste9 and the KEN box in the C terminus of Ams2. We also find that stabilization of Ams2 sensitizes cells to the anti-microtubule drug thiabendazole and the histone deacetylase inhibitor tricostatin A when a histone deacetylase gene hst4 is deleted, suggesting that histone acetylation together with Ams2 stability ensures the coupling of mitosis to DNA replication. Furthermore, in meiosis, the failure of the APC/C-mediated destruction of Ams2 is deleterious, and pre-meiotic DNA replication is barely completed. These data suggest that Ams2 destruction via both the APC/C and the SCF ubiquitin ligases underlies the coordination of histone expression and DNA replication.
authors.affiliation: Cell Cycle Control Group, University College London Cancer Institute, WC1E 6BT, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Trickey
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Fujimitsu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamano
mesh_terms: D000107:Acetylation; D064173:Anaphase-Promoting Complex-Cyclosome; D004261:DNA Replication; D004271:DNA, Fungal / Q000096:biosynthesis* / Q000235:genetics; D016193:G1 Phase; D050980:GATA Transcription Factors / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008540:Meiosis; D059748:Proteolysis; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*; D054875:Ubiquitination
chemical_list: C472167:Ams2 protein, S pombe; D004271:DNA, Fungal; D050980:GATA Transcription Factors; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome