Loss of PICH Results in Chromosomal Instability, P53 Activation, and Embryonic Lethality

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Sep 21

PMID 30232008

Citations 19

Authors

Eliene Albers

Mauro Sbroggio

David Pladevall-Morera

Anna H Bizard

Alexandra Avram

Patricia Gonzalez

Javier Martin-Gonzalez

Ian D Hickson

Andres J Lopez-Contreras

Affiliations

Soon will be listed here.

Abstract

PICH is a DNA translocase necessary for the resolution of ultrafine anaphase DNA bridges and to ensure the fidelity of chromosomal segregation. Here, we report the generation of an animal model deficient for PICH that allowed us to investigate its physiological relevance. Pich KO mice lose viability during embryonic development due to a global accumulation of DNA damage. However, despite the presence of chromosomal instability, extensive p53 activation, and increased apoptosis throughout the embryo, Pich KO embryos survive until day 12.5 of embryonic development. The absence of p53 failed to improve the viability of the Pich KO embryos, suggesting that the observed developmental defects are not solely due to p53-induced apoptosis. Moreover, Pich-deficient mouse embryonic fibroblasts exhibit chromosomal instability and are resistant to RAS/E1A-induced transformation. Overall, our data indicate that PICH is essential to preserve chromosomal integrity in rapidly proliferating cells and is therefore critical during embryonic development and tumorigenesis.

Citing Articles

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