The centromere is essential for the inheritance of genetic information on eukaryotic chromosomes. Epigenetic regulation of centromere identity has been implicated in genome stability, karyotype evolution, and speciation. However, little is known regarding the manner in which centromere dysfunction affects the chromosomal architectures. Here we show that in the fission yeast Schizosaccharomyces pombe, the conditional deletion of the centromere produces survivors that carry either a neocentromere-acquired chromosome at the subtelomeric region or an acentric chromosome rescued by intertelomere fusion with either of the remaining chromosomes. The ratio of neocentromere formation to telomere fusion is considerably decreased by the inactivation of genes involved in RNA interference-dependent heterochromatin formation. By affecting the modes of chromosomal reorganization, the genomic distribution of heterochromatin may influence the fate of karyotype evolution.
CENP-A is a centromere-specific histone H3 variant that is essential for kinetochore formation. Here, we report that the fission yeast Schizosaccharomyces pombe has at least two distinct CENP-A deposition phases across the cell cycle: S and G2. The S phase deposition requires Ams2 GATA factor, which promotes histone gene activation. In ⌬ams2, CENP-A fails to retain during S, but it reaccumulates onto centromeres via the G2 deposition pathway, which is down-regulated by Hip1, a homologue of HIRA histone chaperon. Reducing the length of G2 in ⌬ams2 results in failure of CENP-A accumulation, leading to chromosome missegregation. N-terminal green fluorescent protein-tagging reduces the centromeric association of CENP-A, causing cell death in ⌬ams2 but not in wild-type cells, suggesting that the N-terminal tail of CENP-A may play a pivotal role in the formation of centromeric nucleosomes at G2. These observations imply that CENP-A is normally localized to centromeres in S phase in an Ams2-dependent manner and that the G2 pathway may salvage CENP-A assembly to promote genome stability. The flexibility of CENP-A incorporation during the cell cycle may account for the plasticity of kinetochore formation when the authentic centromere is damaged. INTRODUCTIONThe kinetochore is a multiprotein-DNA complex that is indispensable for chromosome segregation and that normally forms on a single chromosomal locus, the centromere (Cleveland et al., 2003). Lack of a kinetochore or formation of multiple kinetochores on a chromosome may have deleterious effects on mitosis (Karpen and Allshire, 1997;Amor and Choo, 2002;Henikoff and Dalal, 2005). CENP-A represents the most likely candidate for the epigenetic "mark" responsible for the maintenance of centromere identity (Black et al., 2004. Because reformation of CENP-A-containing nucleosomes after DNA synthesis is thought to be a prerequisite for mitotic kinetochore assembly, precise targeting of CENP-A into a single, restricted locus on each chromosome before cell division is essential for cell viability . At least three components that affect CENP-A localization, the Mis16 -Mis18 complex (Hayashi et al., 2004;Fujita et al., 2007), the Mis6 -Sim4 complex (Takahashi et al., 2000;Pidoux et al., 2003), and Ams2 GATA-type transcription factor (Chen et al., 2003a), have been identified in the fission yeast Schizosaccharomyces pombe, which is an ideal model organism in which to study complex centromere structure and function (Takahashi et al., 1992;Karpen and Allshire, 1997).Which phase of the cell cycle is used for CENP-A incorporation remains controversial. During S phase, canonical core histones have been suggested to be deposited into duplicated DNAs in a semiconservative manner (Tagami et al., 2004;Natsume et al., 2007). Experiments using fluorescence recovery after photobleaching demonstrated that CENP-A of the budding yeast Saccharomyces cerevisiae is recruited to centromeres coincident with DNA synthesis (Pearson et al., 2004), presumably reflecting disassembly and reassembly of cent...
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