title: Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells.
abstract: 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.
authors.affiliation: Institut Pasteur, Unité de Génétique Fonctionnelle de la Souris, Département de Biologie du Développement ,  25 rue du docteur Roux, F-75015 Paris ,  France ; CNRS URA 2578, F-75015 Paris ,  France.
authors.forename: Teddy
authors.initials: T
authors.lastname: Léguillier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Vandormael-Pournin
authors.forename: Jérôme
authors.initials: J
authors.lastname: Artus
authors.forename: Martin
authors.initials: M
authors.lastname: Houlard
authors.forename: Christel
authors.initials: C
authors.lastname: Picard
authors.forename: Florence
authors.initials: F
authors.lastname: Bernex
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robine
authors.forename: Michel
authors.initials: M
authors.lastname: Cohen-Tannoudji