ATM in focus: A damage sensor and cancer target

The ability of a cell to conserve and maintain its native DNA sequence is fundamental for the survival and normal functioning of the whole organism and protection from cancer development. Here we review recently obtained results and current topics concerning the role of the ataxiatelangiectasia muta...

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Bibliographic Details
Published inBiodiscovery Vol. 5; pp. 1 - 60
Main Authors Khalil, Hilal, Tummala, Hemanth, Zhelev, Nikolai
Format Journal Article
LanguageEnglish
Published Sofia Pensoft Publishers 01.11.2012
Subjects
Cancer
Cell proliferation
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
Gene regulation
Homologous recombination
Kinases
Mathematical models
Nucleotide sequence
Oxidative stress
Protein kinase
Signal transduction
Therapeutic applications
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Summary:The ability of a cell to conserve and maintain its native DNA sequence is fundamental for the survival and normal functioning of the whole organism and protection from cancer development. Here we review recently obtained results and current topics concerning the role of the ataxiatelangiectasia mutated (ATM) protein kinase as a damage sensor and its potential as therapeutic target for treating cancer. This monograph discusses DNA repair mechanisms activated after DNA doublestrand breaks (DSBs), i.e. nonhomologous end joining, homologous recombination and single strand annealing and the role of ATM in the above types of repair. In addition to DNA repair, ATM participates in a diverse set of physiological processes involving metabolic regulation, oxidative stress, transcriptional modulation, protein degradation and cell proliferation. Full understanding of the complexity of ATM functions and the design of therapeutics that modulate its activity to combat diseases such as cancer necessitates parallel theoretical and experimental efforts. This could be best addressed by employing a systems biology approach, involving mathematical modelling of cell signalling pathways.
ISSN:2050-2966
2050-2966
DOI:10.7750/BioDiscovery.2012.5.1