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

Author

Listed:
  • Andrea Piunti

    (European Institute of Oncology)

  • Alessandra Rossi

    (European Institute of Oncology)

  • Aurora Cerutti

    (IFOM Foundation—FIRC Institute of Molecular Oncology Foundation)

  • Mareike Albert

    (Biotech Research and Innovation, University of Copenhagen
    Centre for Epigenetics, University of Copenhagen)

  • Sriganesh Jammula

    (European Institute of Oncology)

  • Andrea Scelfo

    (European Institute of Oncology)

  • Laura Cedrone

    (European Institute of Oncology
    Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia (IIT))

  • Giulia Fragola

    (European Institute of Oncology
    IFOM Foundation—FIRC Institute of Molecular Oncology Foundation)

  • Linda Olsson

    (Biotech Research and Innovation, University of Copenhagen
    Centre for Epigenetics, University of Copenhagen)

  • Haruhiko Koseki

    (Developmental Genetics Group, RIKEN Research Center for Allergy & Immunology (RCAI), 1-7-22 Suehiuro-cho, Tsurumi)

  • Giuseppe Testa

    (European Institute of Oncology)

  • Stefano Casola

    (IFOM Foundation—FIRC Institute of Molecular Oncology Foundation)

  • Kristian Helin

    (Biotech Research and Innovation, University of Copenhagen
    Centre for Epigenetics, University of Copenhagen
    The Danish Stem Cell Centre, University of Copenhagen)

  • Fabrizio d’Adda di Fagagna

    (IFOM Foundation—FIRC Institute of Molecular Oncology Foundation
    Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche)

  • Diego Pasini

    (European Institute of Oncology)

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.

Suggested Citation

  • Andrea Piunti & Alessandra Rossi & Aurora Cerutti & Mareike Albert & Sriganesh Jammula & Andrea Scelfo & Laura Cedrone & Giulia Fragola & Linda Olsson & Haruhiko Koseki & Giuseppe Testa & Stefano Caso, 2014. "Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4649
    DOI: 10.1038/ncomms4649
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    Cited by:

    1. Junichiro Takano & Shinsuke Ito & Yixing Dong & Jafar Sharif & Yaeko Nakajima-Takagi & Taichi Umeyama & Yong-Woon Han & Kyoichi Isono & Takashi Kondo & Yusuke Iizuka & Tomohiro Miyai & Yoko Koseki & M, 2022. "PCGF1-PRC1 links chromatin repression with DNA replication during hematopoietic cell lineage commitment," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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