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Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability
Previous reports have shown that expression of BARD1δ, a deletion-bearing isoform of BARD1, correlates with tumor aggressiveness and progression. We show that expression of BARD1δ induces cell cycle arrest in vitro and in vivo in non-malignant cells. We investigated the mechanism that leads to proli...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354735/ https://www.ncbi.nlm.nih.gov/pubmed/28030839 http://dx.doi.org/10.18632/oncotarget.14068 |
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author | Pilyugin, Maxim André, Pierre-Alain Ratajska, Magdalena Kuzniacka, Alina Limon, Janusz Tournier, Benjamin B. Colas, Julien Laurent, Geoff Irminger-Finger, Irmgard |
author_facet | Pilyugin, Maxim André, Pierre-Alain Ratajska, Magdalena Kuzniacka, Alina Limon, Janusz Tournier, Benjamin B. Colas, Julien Laurent, Geoff Irminger-Finger, Irmgard |
author_sort | Pilyugin, Maxim |
collection | PubMed |
description | Previous reports have shown that expression of BARD1δ, a deletion-bearing isoform of BARD1, correlates with tumor aggressiveness and progression. We show that expression of BARD1δ induces cell cycle arrest in vitro and in vivo in non-malignant cells. We investigated the mechanism that leads to proliferation arrest and found that BARD1δ overexpression induced mitotic arrest with chromosome and telomere aberrations in cell cultures, in transgenic mice, and in cells from human breast and ovarian cancer patients with BARD1 mutations. BARD1δ binds more efficiently than BARD1 to telomere binding proteins and causes their depletion from telomeres, leading to telomere and chromosomal instability. While this induces cell cycle arrest, cancer cells lacking G2/M checkpoint controls might continue to proliferate despite the BARD1δ-induced chromosomal instability. These features of BARD1δ may make it a genome permutator and a driver of continuous uncontrolled proliferation of cancer cells. |
format | Online Article Text |
id | pubmed-5354735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53547352017-04-14 Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability Pilyugin, Maxim André, Pierre-Alain Ratajska, Magdalena Kuzniacka, Alina Limon, Janusz Tournier, Benjamin B. Colas, Julien Laurent, Geoff Irminger-Finger, Irmgard Oncotarget Research Paper Previous reports have shown that expression of BARD1δ, a deletion-bearing isoform of BARD1, correlates with tumor aggressiveness and progression. We show that expression of BARD1δ induces cell cycle arrest in vitro and in vivo in non-malignant cells. We investigated the mechanism that leads to proliferation arrest and found that BARD1δ overexpression induced mitotic arrest with chromosome and telomere aberrations in cell cultures, in transgenic mice, and in cells from human breast and ovarian cancer patients with BARD1 mutations. BARD1δ binds more efficiently than BARD1 to telomere binding proteins and causes their depletion from telomeres, leading to telomere and chromosomal instability. While this induces cell cycle arrest, cancer cells lacking G2/M checkpoint controls might continue to proliferate despite the BARD1δ-induced chromosomal instability. These features of BARD1δ may make it a genome permutator and a driver of continuous uncontrolled proliferation of cancer cells. Impact Journals LLC 2016-12-21 /pmc/articles/PMC5354735/ /pubmed/28030839 http://dx.doi.org/10.18632/oncotarget.14068 Text en Copyright: © 2017 Pilyugin et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Pilyugin, Maxim André, Pierre-Alain Ratajska, Magdalena Kuzniacka, Alina Limon, Janusz Tournier, Benjamin B. Colas, Julien Laurent, Geoff Irminger-Finger, Irmgard Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability |
title | Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability |
title_full | Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability |
title_fullStr | Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability |
title_full_unstemmed | Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability |
title_short | Antagonizing functions of BARD1 and its alternatively spliced variant BARD1δ in telomere stability |
title_sort | antagonizing functions of bard1 and its alternatively spliced variant bard1δ in telomere stability |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354735/ https://www.ncbi.nlm.nih.gov/pubmed/28030839 http://dx.doi.org/10.18632/oncotarget.14068 |
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