Publication Date:
2015-09-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanno, Yuji -- Susumu, Hiroaki -- Kawamura, Miyuki -- Sugimura, Haruhiko -- Honda, Takashi -- Watanabe, Yoshinori -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1237-40. doi: 10.1126/science.aaa2655.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan. ; 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. ; First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26359403" target="_blank"〉PubMed〈/a〉
Keywords:
BRCA1 Protein/genetics
;
Carcinogenesis/genetics/*metabolism
;
Cell Cycle Proteins/genetics/*metabolism
;
Centromere/genetics/*metabolism
;
Chromatids/metabolism
;
Chromatin/metabolism
;
*Chromosomal Instability
;
Chromosomal Proteins, Non-Histone/metabolism
;
*Chromosome Segregation
;
HeLa Cells
;
Histones/metabolism
;
Humans
;
Kinetochores/metabolism
;
Lysine/metabolism
;
Methylation
;
Microtubules/metabolism
;
Retinoblastoma Protein/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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