edoc

Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control

Thanasopoulou, Angeliki and Stravopodis, Dimitrios J. and Dimas, Konstantinos S. and Schwaller, Juerg and Anastasiadou, Ema. (2012) Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control. PLoS ONE, 7 (2). e31007.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/62078/

Downloads: Statistics Overview

Abstract

In most cancers harboring Ccdc6 gene rearrangements, like papillary thyroid tumors or myeloproliferative disorders, the product of the normal allele is supposed to be functionally impaired or absent. To address the consequence of the loss of CCDC6 expression, we applied lentiviral shRNA in several cell lines. Loss of CCDC6 resulted in increased cell death with clear shortening of the S phase transition of the cell cycle. Upon exposure to etoposide, the cells lacking CCDC6 did not achieve S-phase accumulation. In the absence of CCDC6 and in the presence of genotoxic stress, like etoposide treatment or UV irradiation, increased accumulation of DNA damage was observed, as indicated by a significant increase of pH2Ax Ser139. 14-3-3σ, a major cell cycle regulator, was down-regulated in CCDC6 lacking cells, regardless of genotoxic stress. Interestingly, in the absence of CCDC6, the well-known genotoxic stress-induced cytoplasmic sequestration of the S-phase checkpoint CDC25C phosphatase did not occur. These observations suggest that CCDC6 plays a key role in cell cycle control, maintenance of genomic stability and cell survival and provide a rational of how disruption of CCDC6 normal function contributes to malignancy.
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Kindliche Leukämie (Schwaller)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Kindliche Leukämie (Schwaller)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Childhood Leukemia (Schwaller)
UniBasel Contributors:Schwaller, Jürg
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:28 Jul 2020 12:16
Deposited On:28 Jul 2020 12:16

Repository Staff Only: item control page