Ataxia-telangiectasia and the ATM gene: Linking neurodegeneration, immunodeficiency, and cancer to cell cycle checkpoints

1996 ◽  
Vol 16 (5) ◽  
pp. 254-260 ◽  
Author(s):  
Yosef Shiloh ◽  
Galit Rotman
Keyword(s):  
Cell Cycle ◽  
Ataxia Telangiectasia ◽  
Cell Cycle Checkpoints ◽  
Atm Gene

Multiple defects of cell cycle checkpoints in U937-ASPI3K, an U937 cell mutant stably expressing anti-sense ATM gene cDNA

2000 ◽  
Vol 20 (4) ◽  
pp. 273-276 ◽  
Author(s):  
Zhou Jianfeng ◽  
Liu Wenli ◽  
Sun Lan ◽  
Sun Hanying ◽  
Tang Yi
Keyword(s):  
Cell Cycle ◽  
U937 Cell ◽  
Cell Cycle Checkpoints ◽  
Cell Mutant ◽  
Multiple Defects ◽  
Atm Gene

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 Identification of Two Novel Mutations in the ATM Gene from Patients with Ataxia-Telangiectasia by Whole Exome Sequencing

2020 ◽  
Vol 20 (7) ◽  
pp. 531-534
Author(s):  
Masoud Heidari ◽  
Morteza Soleyman-Nejad ◽  
Mohammad H. Taskhiri ◽  
Javad Shahpouri ◽  
Alireza Isazadeh ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Ataxia Telangiectasia ◽  
Direct Sequencing ◽  
Genetic Diagnosis ◽  
Cell Cycle Checkpoints ◽  
Causative Mutation ◽  
Novel Mutations ◽  
Whole Exome ◽  
Atm Gene

Background: Ataxia telangiectasia (AT) is one of the most common autosomal recessive hereditary ataxia presenting in childhood. The responsible gene for AT designated ATM (AT, mutated) encodes a protein which is involved in cell cycle checkpoints and other responses to genotoxicity. We describe two novel disease-causing mutations in two unrelated Iranian families with Ataxiatelangiectasia. Methods: The probands including a 6-year-old female and an 18-year-old boy were diagnosed with Ataxia-telangiectasia among two different Iranian families. In this study, Whole-Exome Sequencing (WES) was employed for the detection of genetic changes in probands. The analysis of the cosegregation of the variants with the disease in families was conducted using PCR direct sequencing. Results: Two novel frameshift mutations, (c.4236_4236del p. Pro1412fs) and (c.8907T>G p. Tyr2969Ter) in the ataxia telangiectasia mutated ATM gene were detected using Whole-Exome Sequencing (WES) in the probands. These mutations were observed in two separate A-T families. Conclusion: Next-generation sequencing successfully identified the causative mutation in families with ataxia-telangiectasia. These novel mutations in the ATM gene reported in the present study could assist genetic counseling, Preimplantation Genetic Diagnosis (PGD) and prenatal diagnosis (PND) of AT.

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.

Cancer Treatment with Liposomes Based Drugs and Genes Co-delivery Systems

2018 ◽  
Vol 25 (28) ◽  
pp. 3319-3332 ◽  
Author(s):  
Chuanmin Zhang ◽  
Shubiao Zhang ◽  
Defu Zhi ◽  
Jingnan Cui
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Synergistic Effects ◽  
Resistance Mechanisms ◽  
Delivery Systems ◽  
Cell Cycle Checkpoints ◽  
Drug Efflux ◽  
Cancer Resistance ◽  
Cancer Models ◽  
Anti Cancer

There are several mechanisms by which cancer cells develop resistance to treatments, including increasing anti-apoptosis, increasing drug efflux, inducing angiogenesis, enhancing DNA repair and altering cell cycle checkpoints. The drugs are hard to reach curative effects due to these resistance mechanisms. It has been suggested that liposomes based co-delivery systems, which can deliver drugs and genes to the same tumor cells and exhibit synergistic anti-cancer effects, could be used to overcome the resistance of cancer cells. As the co-delivery systems could simultaneously block two or more pathways, this might promote the death of cancer cells by sensitizing cells to death stimuli. This article provides a brief review on the liposomes based co-delivery systems to overcome cancer resistance by the synergistic effects of drugs and genes. Particularly, the synergistic effects of combinatorial anticancer drugs and genes in various cancer models employing multifunctional liposomes based co-delivery systems have been discussed. This review also gives new insights into the challenges of liposomes based co-delivery systems in the field of cancer therapy, by which we hope to provide some suggestions on the development of liposomes based co-delivery systems.

scholarly journals Effect of ATR Inhibition in RT Response of HPV-Negative and HPV-Positive Head and Neck Cancers

2021 ◽  
Vol 22 (4) ◽  
pp. 1504
Author(s):  
Rüveyda Dok ◽  
Mary Glorieux ◽  
Marieke Bamps ◽  
Sandra Nuyts
Keyword(s):  
Head And Neck ◽  
Ataxia Telangiectasia ◽  
Cell Cycle Checkpoints ◽  
Specific Cell ◽  
Ataxia Telangiectasia Mutated ◽  
Checkpoint Kinase 1 ◽  
Hpv Status ◽  
Damage Response ◽  
Xenograft Models ◽  
Potential Use

Radiotherapy (RT) has a central role in head and neck squamous cell carcinoma (HNSCC) treatment. Targeted therapies modulating DNA damage response (DDR) and more specific cell cycle checkpoints can improve the radiotherapeutic response. Here, we assessed the influence of ataxia-telangiectasia mutated and Rad3-related (ATR) inhibition with the ATR inhibitor AZD6738 on RT response in both human papillomavirus (HPV)-negative and HPV-positive HNSCC. We found that ATR inhibition enhanced RT response in HPV-negative and HPV-positive cell lines independent of HPV status. The radiosensitizing effect of AZD6738 was correlated with checkpoint kinase 1 (CHK1)-mediated abrogation of G2/M-arrest. This resulted in the inhibition of RT-induced DNA repair and in an increase in the percentage of micronucleated cells. We validated the enhanced RT response in HPV-negative and HPV-positive xenograft models. These data demonstrate the potential use of ATR inhibition in combination with RT as a treatment option for both HPV-negative and HPV-positive HNSCC patients.

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