Sirt7 stabilizes rDNA heterochromatin through recruitment of DNMT1 and Sirt1

Alessandro Ianni, Soraya Hoelper, Marcus Krueger, Thomas Braun, Eva Bober

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Maintenance of highly compact heterochromatin at ribosomal DNA (rDNA) segments is essential to prevent homologous recombination between rDNA repeats and for preserving genomic stability and nucleolar architecture. Here, we investigated the role of Sirtuin 7 (Sirt7) in the regulation of rDNA chromatin structure, rDNA repeat stability and nucleolar organization. We found that Sirt7 mediates heterochromatin formation at rRNA genes through recruitment of DNA methyltransferase 1 and another member of the sirtuin family, Sirt1. Lack of Sirt7 leads to nucleolar fragmentation associated with hypomethylation of rDNA and hyperacetylation of histones at rDNA loci resulting in rDNA and genomic instability. Our findings suggest a novel role of Sirt7 in preventing cellular transformation by mediating maintenance of rDNA repeats and nucleolar integrity.

Original languageEnglish
Pages (from-to)434-440
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume492
Issue number3
DOIs
StatePublished - 21 Oct 2017
Externally publishedYes

Keywords

  • DNMT1
  • Heterochromatin
  • Nucleolus
  • Sirt1
  • Sirt7
  • rDNA repeats

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