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RETRACTED ARTICLE

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Science. 2015 Sep 11;349(6253):1237-40. doi: 10.1126/science.aaa2655.

The inner centromere-shugoshin network prevents chromosomal instability.

Author information

1
Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
2
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.
3
First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
4
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.

Retraction in

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.

Comment in

PMID:
26359403
DOI:
10.1126/science.aaa2655
[Indexed for MEDLINE]
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