ZNF365 Promotes Stability of Fragile Sites and Telomeres

Zhang, Y., Shin, S. J., Liu, D., Ivanova, E., Foerster, F., Ying, H., Zheng, H., Xiao, Y., Chen, Z., Protopopov, A., Depinho, R. A., Paik, J. H. (June 2013) ZNF365 Promotes Stability of Fragile Sites and Telomeres. Cancer Discovery, 3 (7). pp. 798-811. ISSN 21598274

URL: http://www.ncbi.nlm.nih.gov/pubmed/23776040
DOI: 10.1158/2159-8290.cd-12-0536

Abstract

Critically short telomeres activate cellular senescence or apoptosis, as mediated by the tumor suppressor p53, but in the absence of this checkpoint response, telomere dysfunction engenders chromosomal aberrations and cancer. Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability. Germline polymorphisms in the ZNF365 locus are associated with increased cancer risk, including those associated with telomere dysfunction. On the mechanistic level, ZNF365 suppresses expression of a subset of common fragile sites, including telomeres. In the absence of ZNF365, defective telomeres engage in aberrant recombination of telomere ends, leading to increased telomere sister chromatid exchange and formation of anaphase DNA bridges, including ultra-fine DNA bridges, and ultimately increased cytokinesis failure and aneuploidy. Thus, the p53-ZNF365 axis contributes to genomic stability in the setting of telomere dysfunction.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > telomeres
CSHL Authors:
Communities: CSHL labs > Zheng lab
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: 17 June 2013
Date Deposited: 27 Jun 2013 20:38
Last Modified: 16 Oct 2015 15:35
PMCID: PMC3710545
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28390

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving