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Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication
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 t...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996544/ https://www.ncbi.nlm.nih.gov/pubmed/24728135 http://dx.doi.org/10.1038/ncomms4649 |
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author | Piunti, Andrea Rossi, Alessandra Cerutti, Aurora Albert, Mareike Jammula, Sriganesh Scelfo, Andrea Cedrone, Laura Fragola, Giulia Olsson, Linda Koseki, Haruhiko Testa, Giuseppe Casola, Stefano Helin, Kristian di Fagagna, Fabrizio d’Adda Pasini, Diego |
author_facet | Piunti, Andrea Rossi, Alessandra Cerutti, Aurora Albert, Mareike Jammula, Sriganesh Scelfo, Andrea Cedrone, Laura Fragola, Giulia Olsson, Linda Koseki, Haruhiko Testa, Giuseppe Casola, Stefano Helin, Kristian di Fagagna, Fabrizio d’Adda Pasini, Diego |
author_sort | Piunti, Andrea |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3996544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39965442014-04-24 Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication Piunti, Andrea Rossi, Alessandra Cerutti, Aurora Albert, Mareike Jammula, Sriganesh Scelfo, Andrea Cedrone, Laura Fragola, Giulia Olsson, Linda Koseki, Haruhiko Testa, Giuseppe Casola, Stefano Helin, Kristian di Fagagna, Fabrizio d’Adda Pasini, Diego Nat Commun Article 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. Nature Pub. Group 2014-04-14 /pmc/articles/PMC3996544/ /pubmed/24728135 http://dx.doi.org/10.1038/ncomms4649 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Piunti, Andrea Rossi, Alessandra Cerutti, Aurora Albert, Mareike Jammula, Sriganesh Scelfo, Andrea Cedrone, Laura Fragola, Giulia Olsson, Linda Koseki, Haruhiko Testa, Giuseppe Casola, Stefano Helin, Kristian di Fagagna, Fabrizio d’Adda Pasini, Diego Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication |
title | Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication |
title_full | Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication |
title_fullStr | Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication |
title_full_unstemmed | Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication |
title_short | Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication |
title_sort | polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating dna replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996544/ https://www.ncbi.nlm.nih.gov/pubmed/24728135 http://dx.doi.org/10.1038/ncomms4649 |
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