Limits...
Coupling histone homeostasis to centromere integrity via the ubiquitin-proteasome system.

Takayama Y, Toda T - Cell Div (2010)

Bottom Line: We have found that Ams2 stability varies during the cell cycle, and that the ubiquitin-proteasome pathway is responsible for Ams2 instability.Our results indicate that excess synthesis of core histones outside S phase results in deleterious effects on cell survival.Finally, we address the significance and potential implications of our work from an evolutionary point of view.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cell Biology, Institute of Life Science, Kurume University, 1-1 Hyakunen-kohen, Kurume, Fukuoka 839-0864, Japan. yutakaya@lsi.kurume-u.ac.jp.

ABSTRACT
In many eukaryotes, histone gene expression is regulated in a cell cycle-dependent manner, with a spike pattern at S phase. In fission yeast the GATA-type transcription factor Ams2 is required for transcriptional activation of all the core histone genes during S phase and Ams2 protein levels per se show concomitant periodic patterns. We have recently unveiled the molecular mechanisms underlying Ams2 fluctuation during the cell cycle. We have found that Ams2 stability varies during the cell cycle, and that the ubiquitin-proteasome pathway is responsible for Ams2 instability. Intriguingly, Ams2 proteolysis requires Hsk1-a Cdc7 homologue in fission yeast generally called Dbf4-dependent protein kinase (DDK)-and the SCF ubiquitin ligase containing the substrate receptor Pof3 F-box protein. Here, we discuss why histone synthesis has to occur only during S phase. Our results indicate that excess synthesis of core histones outside S phase results in deleterious effects on cell survival. In particular, functions of the centromere, in which the centromere-specific H3 variant CENP-A usually form centromeric nucleosomes, are greatly compromised. This defect is, at least in part, ascribable to abnormal incorporation of canonical histone H3 into these nucleosomes. Finally, we address the significance and potential implications of our work from an evolutionary point of view.

No MeSH data available.


Related in: MedlinePlus

Ams2 is a cell cycle-regulated GATA type transcription factor. (A) Schematic structure of Ams2. Structural domains homologous to Daxx (green), amino acid stretches rich in arginine and lysine (magenta) and zinc finger motif (blue) are depicted. Amino acid residues surrounding the phosphorylation sites (asterisks) (which are mutated to alanine in M2 and M3 mutants) and CDK phosphorylation consensus motifs (underlined) are also shown. (B) Fluctuation of Ams2 protein levels during the cell cycle. Wild-type cells were synchronised by centrifugal elutriation. The protein or RNA samples collected every 15 min were assayed by western (anti-Ams2, Ams2 W.B) or northern blotting (histone H4, Histone N.B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2910015&req=5

Figure 1: Ams2 is a cell cycle-regulated GATA type transcription factor. (A) Schematic structure of Ams2. Structural domains homologous to Daxx (green), amino acid stretches rich in arginine and lysine (magenta) and zinc finger motif (blue) are depicted. Amino acid residues surrounding the phosphorylation sites (asterisks) (which are mutated to alanine in M2 and M3 mutants) and CDK phosphorylation consensus motifs (underlined) are also shown. (B) Fluctuation of Ams2 protein levels during the cell cycle. Wild-type cells were synchronised by centrifugal elutriation. The protein or RNA samples collected every 15 min were assayed by western (anti-Ams2, Ams2 W.B) or northern blotting (histone H4, Histone N.B).

Mentions: Ams2 was originally identified as one of the multicopy suppressors of the temperature sensitive (ts) cnp1-1 mutant [19], defective in the centromere-specific histone H3 variant CENP-A [22]. Interestingly genomic sequences encompassing canonical histone H4 genes were also isolated as other multicopy suppressors from the same screening. This raised the possibility that Ams2 could be involved in transcriptional control of histone genes. Indeed Ams2 is a member of the GATA factors containing Daxx and zinc finger DNA binding motifs (Figure 1A).


Coupling histone homeostasis to centromere integrity via the ubiquitin-proteasome system.

Takayama Y, Toda T - Cell Div (2010)

Ams2 is a cell cycle-regulated GATA type transcription factor. (A) Schematic structure of Ams2. Structural domains homologous to Daxx (green), amino acid stretches rich in arginine and lysine (magenta) and zinc finger motif (blue) are depicted. Amino acid residues surrounding the phosphorylation sites (asterisks) (which are mutated to alanine in M2 and M3 mutants) and CDK phosphorylation consensus motifs (underlined) are also shown. (B) Fluctuation of Ams2 protein levels during the cell cycle. Wild-type cells were synchronised by centrifugal elutriation. The protein or RNA samples collected every 15 min were assayed by western (anti-Ams2, Ams2 W.B) or northern blotting (histone H4, Histone N.B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2910015&req=5

Figure 1: Ams2 is a cell cycle-regulated GATA type transcription factor. (A) Schematic structure of Ams2. Structural domains homologous to Daxx (green), amino acid stretches rich in arginine and lysine (magenta) and zinc finger motif (blue) are depicted. Amino acid residues surrounding the phosphorylation sites (asterisks) (which are mutated to alanine in M2 and M3 mutants) and CDK phosphorylation consensus motifs (underlined) are also shown. (B) Fluctuation of Ams2 protein levels during the cell cycle. Wild-type cells were synchronised by centrifugal elutriation. The protein or RNA samples collected every 15 min were assayed by western (anti-Ams2, Ams2 W.B) or northern blotting (histone H4, Histone N.B).
Mentions: Ams2 was originally identified as one of the multicopy suppressors of the temperature sensitive (ts) cnp1-1 mutant [19], defective in the centromere-specific histone H3 variant CENP-A [22]. Interestingly genomic sequences encompassing canonical histone H4 genes were also isolated as other multicopy suppressors from the same screening. This raised the possibility that Ams2 could be involved in transcriptional control of histone genes. Indeed Ams2 is a member of the GATA factors containing Daxx and zinc finger DNA binding motifs (Figure 1A).

Bottom Line: We have found that Ams2 stability varies during the cell cycle, and that the ubiquitin-proteasome pathway is responsible for Ams2 instability.Our results indicate that excess synthesis of core histones outside S phase results in deleterious effects on cell survival.Finally, we address the significance and potential implications of our work from an evolutionary point of view.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cell Biology, Institute of Life Science, Kurume University, 1-1 Hyakunen-kohen, Kurume, Fukuoka 839-0864, Japan. yutakaya@lsi.kurume-u.ac.jp.

ABSTRACT
In many eukaryotes, histone gene expression is regulated in a cell cycle-dependent manner, with a spike pattern at S phase. In fission yeast the GATA-type transcription factor Ams2 is required for transcriptional activation of all the core histone genes during S phase and Ams2 protein levels per se show concomitant periodic patterns. We have recently unveiled the molecular mechanisms underlying Ams2 fluctuation during the cell cycle. We have found that Ams2 stability varies during the cell cycle, and that the ubiquitin-proteasome pathway is responsible for Ams2 instability. Intriguingly, Ams2 proteolysis requires Hsk1-a Cdc7 homologue in fission yeast generally called Dbf4-dependent protein kinase (DDK)-and the SCF ubiquitin ligase containing the substrate receptor Pof3 F-box protein. Here, we discuss why histone synthesis has to occur only during S phase. Our results indicate that excess synthesis of core histones outside S phase results in deleterious effects on cell survival. In particular, functions of the centromere, in which the centromere-specific H3 variant CENP-A usually form centromeric nucleosomes, are greatly compromised. This defect is, at least in part, ascribable to abnormal incorporation of canonical histone H3 into these nucleosomes. Finally, we address the significance and potential implications of our work from an evolutionary point of view.

No MeSH data available.


Related in: MedlinePlus