Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR

Prog Biophys Mol Biol. 2019 Oct:147:4-16. doi: 10.1016/j.pbiomolbio.2019.06.003. Epub 2019 Jun 27.

Abstract

ATM, ATR and DNA-PKCs are key effectors of DNA Damage response and have been extensively linked to tumourigenesis and survival of cancer cells after radio/chemotherapy. Despite numerous efforts, the structures of these proteins remained elusive until very recently. The resolution revolution in Cryo-EM allowed for molecular details of these proteins to be seen for the first time. Here we provide a comprehensive review of the structures of ATM, ATR and DNA-PKcs and their complexes and expand with observations springing from our own cryo-EM studies. These observations include a novel conformation of ATR and novel dimeric arrangements of DNA-PKcs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / chemistry*
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • DNA Damage*
  • Humans
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / chemistry*
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / metabolism*

Substances

  • Site-Specific DNA-Methyltransferase (Adenine-Specific)
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins