Detecting ATM-dependent chromatin modification in DNA damage response

Durga Udayakumar, Nobuo Horikoshi, Lopa Mishra, Clayton Hunt, Tej K. Pandita

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationChromatin Protocols
Subtitle of host publicationThird Edition
PublisherSpringer New York
Pages317-336
Number of pages20
ISBN (Electronic)9781493924745
ISBN (Print)9781493924738
DOIs
StatePublished - Mar 31 2015

Keywords

  • Ataxia-telangiectasia
  • Chromatin modification
  • Double-stranded DNA breaks
  • Telomerase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Udayakumar, D., Horikoshi, N., Mishra, L., Hunt, C., & Pandita, T. K. (2015). Detecting ATM-dependent chromatin modification in DNA damage response. In Chromatin Protocols: Third Edition (pp. 317-336). Springer New York. https://doi.org/10.1007/978-1-4939-2474-5_18