Biphasic incorporation of centromeric histone CENP-A in fission yeast.
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 Delta 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 Delta 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 Delta 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.
Takayama
Yuko
Y
Division of Cell Biology, Institute of Life Science, Kurume University, Fukuoka 839-0864, Japan.
Sato
Hiroshi
H
Saitoh
Shigeaki
S
Ogiyama
Yuki
Y
Masuda
Fumie
F
Takahashi
Kohta
K
D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000378:metabolism; D016195:G2 Phase; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016196:S Phase; D012568:Schizosaccharomyces / Q000166:cytology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; C410349:Cnp1 protein, S pombe; D006657:Histones; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D049452:Green Fluorescent Proteins