Chapter category: DNA Surveillance and Repair

Oncogenesis in Ataxia Telangectasia: Roles of ATM, p53, NF‑kB and DDE Recombination Pathogenesis

This chapter appears in the following book:

Molecular Mechanisms
of Ataxia Telangiectasia

Edited by: Shamim I. Ahmad
ISBN: TBA
» Get more information about this book at landesbioscience.com «

Chapter authors:
David H. Dreyfus

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The mechanistic basis of ATM (Ataxia Telangectasis Mutated) protein interactions with DNA hairpin and related double stranded DNA breaks, generated through V(D)J recombination, has been the subject of numerous recent experimental reports and reviews. The novel focus of this review is the potential sources of unresolved or aberrant hairpin formation resulting in oncogenic DNA recombination events rather than the mechanistic role of ATM in the process of V(D)J recombination. Experimental evidence is reviewed regarding the critical role of ATM in sensing and repair of pathogenic hairpin V(D)J‑like recombination events occurring V(D)J RSS (Recombination Signal Sequences) as well as at endogenous transposable element termini and other cryptic V(D)J RSS like sequences in vertebrates. Evidence from recombination associated with transposons in the invertebrate nematode Caenorhabditis elegans, an organism that lacks ATM is also reviewed as a model system for understanding oncogenic consequences of loss of ATM in vertebrates. The tumor suppressor p53 is required for the function of ATM. Since it is apparent that p53 is phylogenetically related to and functionally regulated by coregulatory pathway of NF‑κB transcription factors, potentially the effector functions of ATM could be blocked not only through loss of the ATM gene but also by alterations in p53 and NF‑κB expression. This model suggests the possibility that genomic stress, due to the activation of endogenous transposons and episomal viral pathogens such as Epstein‑Barr Virus (EBV), could specifically trigger complex interacting pathogenic pathways involving NF‑κB and p53 transcription factors interfering with ATM and a phenotype analogous to loss of ATM in cells with functional ATM protein.

David H. Dreyfus
Keren Pharmaceutical

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Additional chapters from this book:

Oncogenesis in Ataxia Telangectasia: Roles of ATM, p53, NF‑kB and DDE Recombination Pathogenesis

David H. Dreyfus

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Chapter category: DNA Surveillance and Repair

Oncogenesis in Ataxia Telangectasia: Roles of ATM, p53, NF‑kB and DDE Recombination Pathogenesis

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