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

Publication date: Available online 27 June 2019Source: Progress in Biophysics and Molecular BiologyAuthor(s): Domagoj Baretic, Taiana Maia de Oliveira, Martina Niess, Paul Wan, Hannah Pollard, Christopher M. Johnson, Caroline Truman, Eileen McCall, David Fisher, Roger Williams, Christopher PhillipsAbstractATM, 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.

Source: Progress in Biophysics and Molecular Biology - June 28, 2019 Category: Molecular Biology Source Type: research