The inner centromere–shugoshin network prevents chromosomal instability

• Autores: Yuji Tanno, Hiroaki Susumu, Miyuki Kawamura
• Localización: Science, ISSN 0036-8075, Vol. 349, Nº 6253, 2015, págs. 1237-1240
• Idioma: inglés
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• Resumen

  • 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.