Inner centromere formation requires hMis14, a trident kinetochore protein that specifically recruits HP1 to human chromosomes.
Centromeric DNA forms two structures on the mitotic chromosome: the kinetochore, which interacts with kinetochore microtubules, and the inner centromere, which connects sister kinetochores. The assembly of the inner centromere is poorly understood. In this study, we show that the human Mis14 (hMis14; also called hNsl1 and DC8) subunit of the heterotetrameric hMis12 complex is involved in inner centromere architecture through a direct interaction with HP1 (heterochromatin protein 1), mediated via a PXVXL motif and a chromoshadow domain. We present evidence that the mitotic function of hMis14 and HP1 requires their functional association at interphase. Alterations in the hMis14 interaction with HP1 disrupt the inner centromere, characterized by the absence of hSgo1 (Shugoshin-like 1) and aurora B. The assembly of HP1 in the inner centromere and the localization of hMis14 at the kinetochore are mutually dependent in human chromosomes. hMis14, which contains a tripartite-binding domain for HP1 and two other kinetochore proteins, hMis13 and blinkin, is a cornerstone for the assembly of the inner centromere and kinetochore.
Core Research for Evolutional Science and Technology Research Program, Japan Science and Technology Corporation, Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Tomomi
T
Kiyomitsu
Osamu
O
Iwasaki
Chikashi
C
Obuse
Mitsuhiro
M
Yanagida
D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002503:Centromere / Q000235:genetics / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D009687:Nuclear Proteins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C532764:DSN1 protein, human; C472643:Knl1 protein, human; C492664:MIS12 protein, human; D008869:Microtubule-Associated Proteins; C574033:NSL1 protein, human; D009687:Nuclear Proteins; D000090266:Chromobox Protein Homolog 5