DNA Damage: Cellular Responses, Repair, and Cancer Treatment

  • Brian M. Cartwright
  • Phillip R. Musich
  • Yue Zou
Chapter
Part of the Current Human Cell Research and Applications book series (CHCRA)

Abstract

The maintenance of genomic stability in the face of endogenous and exogenous sources of DNA damage requires a robust and comprehensive cellular response. This response, appropriately deemed the DNA damage response (DDR), facilitates changes in the cellular environment promoting and coordinating cell cycle arrest, DNA repair, and cell death in cases of extreme or prolonged genomic insult. Initiation of DDR is primarily elicited by three members of the PIKK (phosphatidylinositol-3-kinase-like kinase) family: ATM (ataxia-telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related), and DNA-PK (DNA-dependent protein kinase). While all three are required for proper genomic maintenance, DNA-PK lacks the capacity to elicit many of the effects induced by ATM or ATR. For this reason, DNA damage signaling (DDS) generally is considered to occur mainly through ATM and ATR. Recent studies, however, have implicated that DNA-PK can regulate DDS through hindrance of ATM-DDS, giving rise to an evolving view in which all three PIKK family members are essential for regulation of DDS, but not its initiation. This chapter presents a discussion of the signaling within human systems induced by DNA damage as well as an overview of the roles of DDS in promoting DDR-mediated cell cycle arrest, DNA damage repair, and changes to other cellular processes. Within this context, the roles of DDR in current and proposed chemotherapeutics will be explored.

Keywords

DNA Damage DNA Damage Response Cell Cycle Regulation Cancer Chemotherapeutics 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Brian M. Cartwright
    • 1
  • Phillip R. Musich
    • 1
  • Yue Zou
    • 1
  1. 1.Department of Biomedical Sciences, Quillen College of MedicineEast Tennessee State UniversityJohnson CityUSA

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