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Detecting ATM-Dependent Chromatin Modification in DNA Damage Response

  • Durga Udayakumar
  • Nobuo Horikoshi
  • Lopa Mishra
  • Clayton Hunt
  • Tej K. PanditaEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1288)

Abstract

Loss of function or mutation of the ataxia–telangiectasia mutated gene product (ATM) results in inherited genetic disorders characterized by neurodegeneration, immunodeficiency, and cancer. Ataxia-telangiectasia mutated (ATM) gene product belongs to the PI3K-like protein kinase (PIKKs) family and is functionally implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination, cell-cycle control, and telomere maintenance. The ATM protein kinase is primarily activated in response to DNA double strand breaks (DSBs), the most deleterious form of DNA damage produced by ionizing radiation (IR) or radiomimetic drugs. It is detected at DNA damage sites, where ATM autophosphorylation causes dissociation of the inactive homodimeric form to the activated monomeric form. Interestingly, heat shock can activate ATM independent of the presence of DNA strand breaks. ATM is an integral part of the sensory machinery that detects DSBs during meiosis, mitosis, or DNA breaks mediated by free radicals. These DNA lesions can trigger higher order chromatin reorganization fuelled by posttranslational modifications of histones and histone binding proteins. Our group, and others, have shown that ATM activation is tightly regulated by chromatin modifications. This review summarizes the multiple approaches used to discern the role of ATM and other associated proteins in chromatin modification in response to DNA damage.

Key words

Ataxia–telangiectasia Telomerase Double-stranded DNA breaks Chromatin modification 

Notes

Acknowledgments

The authors thank the former and current members of the laboratory, who have carried out the work presented in this manuscript. We thank all the colleagues around the world whose scientific contributions helped to write this article. This work was supported by funds from several NIH grants including CA129537 (TKP) and CA154320 (TKP).

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Durga Udayakumar
    • 1
  • Nobuo Horikoshi
    • 1
  • Lopa Mishra
    • 2
  • Clayton Hunt
    • 1
  • Tej K. Pandita
    • 3
    Email author
  1. 1.Department of Radiation OncologyHouston Methodist Research InstituteHoustonUSA
  2. 2.Department of GastroenterologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Radiation OncologyHouston Methodist Research InstituteHoustonUSA

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