ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors

Sayaka Ueno, Tamotsu Sudo, Akira Hirasawa

Research output: Contribution to journalReview articlepeer-review

Abstract

Ataxia–telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.

Original languageEnglish
Article number523
JournalInternational journal of molecular sciences
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 1 2022
Externally publishedYes

Keywords

  • ATM
  • DNA damage
  • Hereditary tumors
  • Precision therapy
  • Redox homeostasis
  • Tumor profiling

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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