Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication

Andrea Piunti, Alessandra Rossi, Aurora Cerutti, Mareike Albert, Sriganesh Jammula, Andrea Scelfo, Laura Cedrone, Giulia Fragola, Linda Olsson, Haruhiko Koseki, Giuseppe Testa, Stefano Casola, Kristian Helin, Fabrizio D Adda Di Fagagna, Diego Pasini

Research output: Contribution to journalArticle

Abstract

The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity to cancer. PcGs silence the expression of the tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53 functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG inhibition has been proposed as a strategy for cancer treatment. However, the recurrent inactivation of pRb/p53 responses in human cancers raises a question regarding the ability of PcG proteins to affect cellular proliferation independently from this checkpoint. Here we demonstrate that PRCs regulate cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53 pathway. We provide evidence that PRCs localize at replication forks, and that loss of their function directly affects the progression and symmetry of DNA replication forks. Thus, we have identified a novel activity by which PcGs can regulate cell proliferation independently of major cell cycle restriction checkpoints.

Original languageEnglish
Article number3649
JournalNature Communications
Volume5
DOIs
Publication statusPublished - Apr 14 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

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    Piunti, A., Rossi, A., Cerutti, A., Albert, M., Jammula, S., Scelfo, A., Cedrone, L., Fragola, G., Olsson, L., Koseki, H., Testa, G., Casola, S., Helin, K., Di Fagagna, F. D. A., & Pasini, D. (2014). Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication. Nature Communications, 5, [3649]. https://doi.org/10.1038/ncomms4649