DNA-dependent protein kinase in telomere maintenance and protection

Cell Mol Biol Lett. 2020 Jan 17;25:2. doi: 10.1186/s11658-020-0199-0. eCollection 2020.

Abstract

This review focuses on DNA-dependent protein kinase (DNA-PK), which is the key regulator of canonical non-homologous end-joining (NHEJ), the predominant mechanism of DNA double-strand break (DSB) repair in mammals. DNA-PK consists of the DNA-binding Ku70/80 heterodimer and the catalytic subunit DNA-PKcs. They assemble at DNA ends, forming the active DNA-PK complex, which initiates NHEJ-mediated DSB repair. Paradoxically, both Ku and DNA-PKcs are associated with telomeres, and they play crucial roles in protecting the telomere against fusions. Herein, we discuss possible mechanisms and contributions of Ku and DNA-PKcs in telomere regulation.

Keywords: DNA–PK; Shelterin; Telomerase; Telomere; hnRNP–A1.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA End-Joining Repair / genetics
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Activated Protein Kinase / chemistry
  • DNA-Activated Protein Kinase / genetics
  • DNA-Activated Protein Kinase / metabolism*
  • Heterogeneous Nuclear Ribonucleoprotein A1 / metabolism*
  • Humans
  • Ku Autoantigen / metabolism
  • Telomerase / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere-Binding Proteins / metabolism*

Substances

  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Telomere-Binding Proteins
  • shelterin, human
  • DNA-Activated Protein Kinase
  • Telomerase
  • Ku Autoantigen
  • DNA Topoisomerases, Type II