The inner centromere–shugoshin network prevents chromosomal instability

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2015-09, Vol.349 (6253), p.1237-1240
Main Authors: Tanno, Yuji, Susumu, Hiroaki, Kawamura, Miyuki, Sugimura, Haruhiko, Honda, Takashi, Watanabe, Yoshinori
Format: Article
Language:English
Subjects:
Cancer
Cell division
Chromosomes
Cohesion
Histones
Instability
Lysine
Molecular biology
Networks
Stability
Tumorigenesis
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaa2655