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The chromatin remodelling complex NoRC safeguards genome stability by heterochromatin formation at telomeres and centromeres
Authors:Anna Postepska-Igielska  Damir Krunic  Nina Schmitt  Karin M Greulich-Bode  Petra Boukamp  Ingrid Grummt
Institution:1Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, INF 581, D-69120 Heidelberg, Germany;2Division of Genetics of Skin Carcinogenesis, German Cancer Research Center, DKFZ-ZMBH Alliance, INF 581, D-69120 Heidelberg, Germany
Abstract:Constitutive heterochromatin is crucial for the integrity of chromosomes and genomic stability. Here, we show that the chromatin remodelling complex NoRC, known to silence a fraction of rRNA genes, also establishes a repressive heterochromatic structure at centromeres and telomeres, preserving the structural integrity of these repetitive loci. Knockdown of NoRC leads to relaxation of centromeric and telomeric heterochromatin, abnormalities in mitotic spindle assembly, impaired chromosome segregation and enhanced chromosomal instability. The results demonstrate that NoRC safeguards genomic stability by coordinating enzymatic activities that establish features of repressive chromatin at centromeric and telomeric regions, and this heterochromatic structure is required for sustaining genomic integrity.
Keywords:NoRC  heterochromatin  telomeres  centromeres  genome stability
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