Structural insights into the critical DNA damage sensors DNA-PKcs, ATM and ATR. (October 2019)

• Record Type: Journal Article
• Authors: Baretic, Domagoj; Maia de Oliveira, Taiana; Niess, Martina; Wan, Paul; Pollard, Hannah; Johnson, Christopher M.; Truman, Caroline; McCall, Eileen; Fisher, David; Williams, Roger; Phillips, Christopher
• Is Part Of: Progress in biophysics and molecular biology. Volume 147(2019)
• Page Start: 4
• Page End: 16
• Publication Date: 2019-10
• Subjects: Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2019.06.003
• Languages: English
• ISSNs: 0079-6107

Abstract

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.