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ATM protein kinase: the linchpin of cellular defenses to stress

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Abstract

ATM is the most significant molecule involved in monitoring the genomic integrity of the cell. Any damage done to DNA relentlessly challenges the cellular machinery involved in recognition, processing and repair of these insults. ATM kinase is activated early to detect and signal lesions in DNA, arrest the cell cycle, establish DNA repair signaling and faithfully restore the damaged chromatin. ATM activation plays an important role as a barrier to tumorigenesis, metabolic syndrome and neurodegeneration. Therefore, studies of ATM-dependent DNA damage signaling pathways hold promise for treatment of a variety of debilitating diseases through the development of new therapeutics capable of modulating cellular responses to stress. In this review, we have tried to untangle the complex web of ATM signaling pathways with the purpose of pinpointing multiple roles of ATM underlying the complex phenotypes observed in AT patients.

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Abbreviations

A-T:

Ataxia-telangiectasia

ATM:

Ataxia-telangiectasia, mutated protein

DNA Dsb:

DNA double-strand breaks

MRN:

Mre11/Rad50/Nbs1 complex

HR:

Homologous recombination

NHEJ:

Non-homologous end-joining

ROS:

Reactive oxygen species

HAT:

Histone acetyltransferase

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Acknowledgments

We apologize to our colleagues whose data have not been cited due to space limitations. The support by grants from the National Health and Medical Research Council (NHMRC), Australian Research Council (ARC) and Cancer Council Queensland (CCQ) is gratefully appreciated. We are thankful to Madeleine Kersting for excellent graphic artwork preparation, Dr Kevin Spring for useful comments and the editor for inviting this review.

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Authors and Affiliations

  1. Institute of Molecular Biology and Biotechnology, The University of Lahore, 1 Km Raiwind Road, Thokar Niaz Baig, Lahore, Pakistan

    Shahzad Bhatti, Ammad Ahmad Farooqi & Ali Naqi

  2. Queensland Institute of Medical Research, QIMR, 300 Herston Rd, Herston, Brisbane, 4029, Australia

    Sergei Kozlov, Martin Lavin & Kum Kum Khanna

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  1. Shahzad Bhatti
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  2. Sergei Kozlov
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  3. Ammad Ahmad Farooqi
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  4. Ali Naqi
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  5. Martin Lavin
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  6. Kum Kum Khanna
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Corresponding author

Correspondence to Sergei Kozlov.

Additional information

S. Bhatti, S. Kozlov and A. A. Farooqi contributed equally to this review.

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Bhatti, S., Kozlov, S., Farooqi, A.A. et al. ATM protein kinase: the linchpin of cellular defenses to stress. Cell. Mol. Life Sci. 68, 2977–3006 (2011). https://doi.org/10.1007/s00018-011-0683-9

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  • DOI: https://doi.org/10.1007/s00018-011-0683-9

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