title: RETRACTED: The inner centromere-shugoshin network prevents chromosomal instability.
abstract: Chromosomal instability (CIN) is a major trait of cancer cells and a potent driver of tumor progression. However, the molecular mechanisms underlying CIN still remain elusive. We found that a number of CIN(+) cell lines have impairments in the integrity of the conserved inner centromere-shugoshin (ICS) network, which coordinates sister chromatid cohesion and kinetochore-microtubule attachment. These defects are caused mostly by the loss of histone H3 lysine 9 trimethylation at centromeres and sometimes by a reduction in chromatin-associated cohesin; both pathways separately sustain centromeric shugoshin stability. Artificial restoration of the ICS network suppresses chromosome segregation errors in a wide range of CIN(+) cells, including RB- and BRCA1-deficient cells. Thus, dysfunction of the ICS network might be a key mechanism underlying CIN in human tumorigenesis.
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanno
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan. Department of Biological Sciences, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Susumu
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan. Department of Biological Sciences, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.affiliation: Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan. Department of Biological Sciences, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan. ywatanab@iam.u-tokyo.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000235:genetics / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008870:Microtubules / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics; D000097722:Cohesins
chemical_list: D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D008239:Lysine; D016160:Retinoblastoma Protein; D000097722:Cohesins; C496644:SGO1 protein, human