Structural insights into the activation of ATM kinase

摘要：

Dear Editor,ATM (ataxia telangiectasia-mutated) is a master regulator in response to DNA damage and activates downstream pathways involved in cell cycle checkpoints,DNA damage repair,transcription regulation,immune response,central nervous system development and metabolism.1,2 Loss of ATM activity in human results in the pleiotropic neurodegeneration disorder ataxia-telangiectasia (A-T) that is characterized by immunodeficiency,cancer predisposition,premature aging and insulin-resistant diabetes.3-5 Despite extensive studies over the past two decades,6,7 it remains controversial how ATM is activated.Particularly,whether ATM exists in a monomeric form,whether the monomer is more active than dimer,and how dimer-to-monomer transition affects the ATM kinase activity,remain controversial.

所属期刊栏目：29

资助基金：We thank Center for Biological Imaging CBI of institute of Biophysics IBP of Chinese Academy of Sciences;National Center for Protein Science Shanghai NCPSSfor the support on cryo-EM data collection and data analyses.We thank staff members working in Biomedical Core Facility,Fudan University for their help on Mass Spectrometry analyses.This work was supported by grants from the Ministry of Science and2016YFA0500700;the National Natural Science Foundation of China31830107,31821002,31425008;the National Program for support of Top-Notch Young Professionals;the Strategic Priority Research Program of the Chinese Academy of Sciencesgrant no.XDB08000000;the UK Wellcome Trust Investigator Award 206422/Z/17/Z P.Z..We acknowledge Diamond for access of the Cryo-EM facilities at the UK national electron bio-imaging centreeBIC,proposal NT21004;funded by the Wellcome Trust,MRC and BBSRC

在线出版日期：2019-09-09（万方平台首次上网日期，不代表论文的发表时间）

页数：共3页

页码：683-685