scholarly journals Defect in Multiple Cell Cycle Checkpoints in Ataxia-Telangiectasia Postirradiation

1996 ◽  
Vol 271 (34) ◽  
pp. 20486-20493 ◽  
Author(s):  
Heather Beamish ◽  
Richard Williams ◽  
Philip Chen ◽  
Martin F. Lavin
Keyword(s):  
Cell Cycle ◽  
Ataxia Telangiectasia ◽  
Cell Cycle Checkpoints ◽  
Multiple Cell

scholarly journals Nuclear Survivin Abrogates Multiple Cell Cycle Checkpoints and Enhances Viral Oncolysis

2008 ◽  
Vol 68 (19) ◽  
pp. 7923-7931 ◽  
Author(s):  
Claire M. Connell ◽  
Sally P. Wheatley ◽  
Iain A. McNeish
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Checkpoints ◽  
Viral Oncolysis ◽  
Multiple Cell ◽  
Nuclear Survivin

scholarly journals ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes

Blood ◽  
2011 ◽  
Vol 117 (8) ◽  
pp. 2441-2450 ◽  
Author(s):  
Krystyna Mazan-Mamczarz ◽  
Patrick R. Hagner ◽  
Yongqing Zhang ◽  
Bojie Dai ◽  
Elin Lehrmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Rna Binding ◽  
Critical Role ◽  
Cell Cycle Checkpoints ◽  
Dependent Manner ◽  
Damage Response ◽  
Multiple Cell

Abstract Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell-cycle checkpoints and DNA repair after DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression posttranscriptionally. Dysregulation of this DNA damage response RNA operon is probably relevant to lymphoma development in ataxia-telangiectasia persons. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.

A multifaceted role for ATM in genome maintenance

2003 ◽  
Vol 5 (16) ◽  
pp. 1-21 ◽  
Author(s):  
Tej K. Pandita
Keyword(s):  
Cell Cycle ◽  
Ataxia Telangiectasia ◽  
Cell Cycle Control ◽  
Cell Cycle Checkpoints ◽  
Telomere Maintenance ◽  
Loss Of Function ◽  
Genome Maintenance ◽  
Ataxia Telangiectasia Mutated ◽  
Gonadal Atrophy ◽  
Mitogenic Signal Transduction

The pleiotropic nature of the clinical phenotypes of patients with ataxia-telangiectasia (A-T) – which encompass cerebellar degeneration (leading to ataxia), gonadal atrophy, and cancer predisposition – suggests multiple functions of the gene responsible for the disease. The ataxia-telangiectasia mutated gene product (ATM), whose loss of function is responsible for ataxia-telangiectasia, is a protein kinase that interacts with several substrates and is implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination, cell-cycle control and telomere maintenance. This review focuses on the critical roles that ATM appears to play in cell-cycle checkpoints, DNA repair, telomere metabolism and oxidative stress, indicating how defects in these processes might lead to ataxia-telangiectasia.

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