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The Schizosaccharomyces pombe HIRA-like protein Hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres

Cell and Molecular Biosciences, University of Newcastle upon Tyne, Newcastle NE2 4HH, United Kingdom.
Molecular and Cellular Biology (Impact Factor: 5.04). 06/2004; 24(10):4309-20. DOI: 10.1128/MCB.24.10.4309-4320.2004
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ABSTRACT HIRA-like (Hir) proteins are evolutionarily conserved and are implicated in the assembly of repressive chromatin. In Saccharomyces cerevisiae, Hir proteins contribute to the function of centromeres. However, S. cerevisiae has point centromeres that are structurally different from the complex centromeres of metazoans. In contrast, Schizosaccharomyces pombe has complex centromeres whose domain structure is conserved with that of human centromeres. Therefore, we examined the functions of the fission yeast Hir proteins Slm9 and the previously uncharacterised protein Hip1. Deletion of hip1(+) resulted in phenotypes that were similar to those described previously for slm9 Delta cells: a cell cycle delay, synthetic lethality with cdc25-22, and poor recovery from nitrogen starvation. However, while it has previously been shown that Slm9 is not required for the periodic expression of histone H2A, we found that loss of Hip1 led to derepression of core histone genes expression outside of S phase. Importantly, we found that deletion of either hip1(+) or slm9(+) resulted in increased rates of chromosome loss, increased sensitivity to spindle damage, and reduced transcriptional silencing in the outer centromeric repeats. Thus, S. pombe Hir proteins contribute to pericentromeric heterochromatin, and our data thus suggest that Hir proteins may be required for the function of metazoan centromeres.

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    • "The importance of the HIR complex is seen by its evolutionary conservation , as it is found in several species, including yeasts, Arabidopsis, Drosophila, Xenopus, chicken, fish, mice and humans [25] [26] [27] [28] [29] [30] [31] [32]. In the fission yeast S. pombe, the HIRA complex is composed of Hip1, Slm9, Hip3 and Hip4 which are homologues of Hir1, Hir2, Hir3 and Hpc2, respectively [33] [34] [35]. The human HIRA protein is the homologue of Hir1 and Hir2 and is required for histone H3.3 deposition at active genes independently of DNA replication [25,36–38]. "
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