Structures and regulations of ATM and ATR, master kinases in genome integrity.

Rhys M Williams, Luke A Yates, Xiaodong Zhang

Journal: Current opinion in structural biology 2021;61():98-105

PMID: 31924595

Full Text on Elsevier Science View on PubMed

Abstract

Homologous recombination (HR) is a faithful repair mechanism for double stranded DNA breaks. Two highly homologous master kinases, the tumour suppressors ATM and ATR (Tel1 and Mec1 in yeast), coordinate cell cycle progression with repair during HR. Despite their importance, our molecular understanding of these apical coordinators has been limited, in part due to their large sizes. With the recent development in cryo-electron microscopy, significant advances have been made in structural characterisation of these proteins in the last two years. These structures, combined with new biochemical studies, now provide a more detailed understanding of how a low basal activity is maintained and how activation may occur. In this review, we summarize recent advances in the structural and molecular understanding of these key components in HR, compare the common and distinct features of these kinases and suggest aspects of structural components that are likely to be involved in regulating its activity.

Address: Section of Structural Biology, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.; Section of Structural Biology, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK. Electronic address: [email protected].

DOI: 10.1016/j.sbi.2019.12.010