Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms4649
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Funding
- Italian Association for Cancer Research
- Italian Ministry of Health
- FIRC (the Italian Foundation for Cancer Research)
- Danish Cancer Society
- Novo Nordisk Foundation
- Danish National Research Foundation
- European Research Council (ERC) Advanced
- EMBO
- FIR
- CAIRC (Associazione Italiana per la Ricerca sul Cancro)
- HFSP (Human Frontier Science Program)
- Cariplo Foundation
- FP7 PEOPLE ITN (CodAge)
- Italian Ministry of University and Research (MIUR) EPIGEN Project
- European Research Council (ERC) Advanced Grant
- AIRC
- AICR
- Worldwide Cancer Research [13-0211] Funding Source: researchfish
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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.
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