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


Journal

Progress in biophysics and molecular biology
ISSN: 1873-1732
Titre abrégé: Prog Biophys Mol Biol
Pays: England
ID NLM: 0401233

Informations de publication

Date de publication:
10 2019
Historique:
received: 22 05 2019
accepted: 24 06 2019
pubmed: 1 7 2019
medline: 19 5 2020
entrez: 1 7 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31255703
pii: S0079-6107(19)30119-1
doi: 10.1016/j.pbiomolbio.2019.06.003
pii:
doi:

Substances chimiques

Site-Specific DNA-Methyltransferase (Adenine-Specific) EC 2.1.1.72
ATR protein, human EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

4-16

Subventions

Organisme : Medical Research Council
ID : MC_U105184308
Pays : United Kingdom

Informations de copyright

Copyright © 2019. Published by Elsevier Ltd.

Auteurs

Domagoj Baretic (D)

Laboratory of Molecular Biology - MRC, Cambridge, UK. Electronic address: domi@mrc-lmb.cam.ac.uk.

Taiana Maia de Oliveira (T)

Structure Biophysics and FBLG, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK. Electronic address: taiana.maiadeoliveira@astrazeneca.com.

Martina Niess (M)

Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK.

Paul Wan (P)

Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK.

Hannah Pollard (H)

Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK.

Christopher M Johnson (CM)

Laboratory of Molecular Biology - MRC, Cambridge, UK.

Caroline Truman (C)

Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK.

Eileen McCall (E)

Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK.

David Fisher (D)

Discovery Biology, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK.

Roger Williams (R)

Laboratory of Molecular Biology - MRC, Cambridge, UK.

Christopher Phillips (C)

Structure Biophysics and FBLG, Discovery Sciences, Biopharmaceuticals R&D, Cambridge, UK.

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Classifications MeSH