Unknown

Dataset Information

0

Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer.

ABSTRACT: Chk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity. Mus81(?ex3-4/?ex3-4) mice have increased cancer susceptibility that is exacerbated by p53 inactivation. In this study, we demonstrate that Chk2 inactivation impairs the development of Mus81(?ex3-4/?ex3-4) lymphoid cells in a cell-autonomous manner. Importantly, in contrast to its predicted tumor suppressor function, loss of Chk2 promotes mitotic catastrophe and cell death, and it results in suppressed oncogenic transformation and tumor development in Mus81(?ex3-4/?ex3-4) background. Thus, our data indicate that an important role for Chk2 is maintaining lymphocyte development and that dual inactivation of Chk2 and Mus81 remarkably inhibits cancer.

SUBMITTER: El Ghamrasni S 

PROVIDER: S-EPMC3098187 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer.

El Ghamrasni Samah S   Pamidi Ashwin A   Halaby Marie Jo MJ   Bohgaki Miyuki M   Cardoso Renato R   Li Li L   Venkatesan Shriram S   Sethu Swaminathan S   Hirao Atsushi A   Mak Tak W TW   Hande Manoor Prakash MP   Hakem Anne A   Hakem Razqallah R  

PLoS genetics 20110519 5

Chk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity. Mus81(Δex3-4/Δex3-4) mice have increased cancer susceptibility that is exacerbated by p53 inactivation. In this study, we demonstrate that Chk2 inactivation impairs the development of Mus81(Δex3-4/Δex3-4) lymphoid cells in a cell-autonomous manner. Importantly, in contrast to its  ...[more]

Similar Datasets

Unknown Standardization of Cell Culture Conditions and Routine Genomic Screening under a Quality Management System Leads to Reduced Genomic Instability in hPSCs.
| S-EPMC9265327 | biostudies-literature
Unknown The presence of extra chromosomes leads to genomic instability.
| S-EPMC4756715 | biostudies-literature
Unknown SPOP mutation leads to genomic instability in prostate cancer.
| S-EPMC4621745 | biostudies-literature
Unknown Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication.
| S-EPMC8331182 | biostudies-literature
Unknown Oxidation of phosphorothioate DNA modifications leads to lethal genomic instability.
| S-EPMC5577368 | biostudies-literature
Unknown Histone demethylase JARID1C inactivation triggers genomic instability in sporadic renal cancer.
| S-EPMC4665784 | biostudies-literature
Unknown LKB1 inactivation leads to centromere defects and genome instability via p53-dependent upregulation of survivin.
| S-EPMC7425461 | biostudies-literature
Unknown Recurring genomic structural variation leads to clonal instability and loss of productivity.
| S-EPMC7058117 | biostudies-literature
Unknown Rint1 inactivation triggers genomic instability, ER stress and autophagy inhibition in the brain.
| S-EPMC5072440 | biostudies-literature
Unknown Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype.
| S-EPMC3134285 | biostudies-literature