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Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells

Recent studies have shown that factors involved in transcription-coupled mRNA processing are important for the maintenance of genome integrity. How these processes are linked and regulated in vivo remains largely unknown. In this study, we addressed in the mouse model the function of Omcg1, which ha...

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Autores principales: Léguillier, Teddy, Vandormael-Pournin, Sandrine, Artus, Jérôme, Houlard, Martin, Picard, Christel, Bernex, Florence, Robine, Sylvie, Cohen-Tannoudji, Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507298/
https://www.ncbi.nlm.nih.gov/pubmed/23213458
http://dx.doi.org/10.1242/bio.20121248
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author Léguillier, Teddy
Vandormael-Pournin, Sandrine
Artus, Jérôme
Houlard, Martin
Picard, Christel
Bernex, Florence
Robine, Sylvie
Cohen-Tannoudji, Michel
author_facet Léguillier, Teddy
Vandormael-Pournin, Sandrine
Artus, Jérôme
Houlard, Martin
Picard, Christel
Bernex, Florence
Robine, Sylvie
Cohen-Tannoudji, Michel
author_sort Léguillier, Teddy
collection PubMed
description Recent studies have shown that factors involved in transcription-coupled mRNA processing are important for the maintenance of genome integrity. How these processes are linked and regulated in vivo remains largely unknown. In this study, we addressed in the mouse model the function of Omcg1, which has been shown to participate in co-transcriptional processes, including splicing and transcription-coupled repair. Using inducible mouse models, we found that Omcg1 is most critically required in intestinal progenitors. In absence of OMCG1, proliferating intestinal epithelial cells underwent abnormal mitosis followed by apoptotic cell death. As a consequence, the crypt proliferative compartment of the small intestine was quickly and totally abrogated leading to the rapid death of the mice. Lack of OMCG1 in embryonic stem cells led to a similar cellular phenotype, with multiple mitotic defects and rapid cell death. We showed that mutant intestinal progenitors and embryonic stem cells exhibited a reduced cell cycle arrest following irradiation, suggesting that mitotic defects may be consecutive to M phase entry with unrepaired DNA damages. These findings unravel a crucial role for pre-mRNA processing in the homeostasis of the small intestine and point to a major role of OMCG1 in the maintenance of genome integrity.
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spelling pubmed-35072982012-12-04 Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells Léguillier, Teddy Vandormael-Pournin, Sandrine Artus, Jérôme Houlard, Martin Picard, Christel Bernex, Florence Robine, Sylvie Cohen-Tannoudji, Michel Biol Open Research Article Recent studies have shown that factors involved in transcription-coupled mRNA processing are important for the maintenance of genome integrity. How these processes are linked and regulated in vivo remains largely unknown. In this study, we addressed in the mouse model the function of Omcg1, which has been shown to participate in co-transcriptional processes, including splicing and transcription-coupled repair. Using inducible mouse models, we found that Omcg1 is most critically required in intestinal progenitors. In absence of OMCG1, proliferating intestinal epithelial cells underwent abnormal mitosis followed by apoptotic cell death. As a consequence, the crypt proliferative compartment of the small intestine was quickly and totally abrogated leading to the rapid death of the mice. Lack of OMCG1 in embryonic stem cells led to a similar cellular phenotype, with multiple mitotic defects and rapid cell death. We showed that mutant intestinal progenitors and embryonic stem cells exhibited a reduced cell cycle arrest following irradiation, suggesting that mitotic defects may be consecutive to M phase entry with unrepaired DNA damages. These findings unravel a crucial role for pre-mRNA processing in the homeostasis of the small intestine and point to a major role of OMCG1 in the maintenance of genome integrity. The Company of Biologists 2012-05-23 /pmc/articles/PMC3507298/ /pubmed/23213458 http://dx.doi.org/10.1242/bio.20121248 Text en © 2012 The Company of Biologists http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Article
Léguillier, Teddy
Vandormael-Pournin, Sandrine
Artus, Jérôme
Houlard, Martin
Picard, Christel
Bernex, Florence
Robine, Sylvie
Cohen-Tannoudji, Michel
Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells
title Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells
title_full Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells
title_fullStr Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells
title_full_unstemmed Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells
title_short Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells
title_sort omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507298/
https://www.ncbi.nlm.nih.gov/pubmed/23213458
http://dx.doi.org/10.1242/bio.20121248
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