Structures and regulations of ATM and ATR, master kinases in genome integrity
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Published version
Author(s)
Williams, Rhys
Yates, Luke
Zhang, Xiaodong
Type
Journal Article
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.
Date Issued
2020-04-01
Date Acceptance
2019-12-07
Citation
Current Opinion in Structural Biology, 2020, 61, pp.98-105
ISSN
0959-440X
Publisher
Elsevier
Start Page
98
End Page
105
Journal / Book Title
Current Opinion in Structural Biology
Volume
61
Copyright Statement
©2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC-BY license (http://creativecommons.org/licenses/by/4.0/
Sponsor
Wellcome Trust
Wellcome Trust
Grant Number
210658/Z/18/Z
204834/Z/16/Z
Subjects
Biophysics
0601 Biochemistry and Cell Biology
0801 Artificial Intelligence and Image Processing
0304 Medicinal and Biomolecular Chemistry
Publication Status
Published
Date Publish Online
2020-01-07