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A more recent version of this article appeared on February 1, 2008
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Submitted on May 29, 2007
Revised on November 12, 2007
Accepted on November 27, 2007
Division of Cell Biology, Institute of Life Science, Kurume University, Fukuoka 839-0864, Japan
Monitoring Editor: Kerry Bloom
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 homolog of HIRA histone chaperon. Reducing the length of G2 in
ams2 results in failure of CENP-A accumulation, leading to chromosome missegregation. N-terminal GFP-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.