Activation of the ATR kinase by the RPA-binding protein ETAA1

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Activation of the ATR kinase by the RPA-binding protein ETAA1. / Haahr, Peter; Hoffmann, Saskia; Tollenaere, Maxim A X; Ho, Teresa; Toledo Lazaro, Luis Ignacio; Mann, Matthias; Bekker-Jensen, Simon; Räschle, Markus; Mailand, Niels.

In: Nature Cell Biology, Vol. 18, No. 11, 11.2016, p. 1196–1207.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Haahr, P, Hoffmann, S, Tollenaere, MAX, Ho, T, Toledo Lazaro, LI, Mann, M, Bekker-Jensen, S, Räschle, M & Mailand, N 2016, 'Activation of the ATR kinase by the RPA-binding protein ETAA1', Nature Cell Biology, vol. 18, no. 11, pp. 1196–1207. https://doi.org/10.1038/ncb3422

APA

Haahr, P., Hoffmann, S., Tollenaere, M. A. X., Ho, T., Toledo Lazaro, L. I., Mann, M., Bekker-Jensen, S., Räschle, M., & Mailand, N. (2016). Activation of the ATR kinase by the RPA-binding protein ETAA1. Nature Cell Biology, 18(11), 1196–1207. https://doi.org/10.1038/ncb3422

Vancouver

Haahr P, Hoffmann S, Tollenaere MAX, Ho T, Toledo Lazaro LI, Mann M et al. Activation of the ATR kinase by the RPA-binding protein ETAA1. Nature Cell Biology. 2016 Nov;18(11):1196–1207. https://doi.org/10.1038/ncb3422

Author

Haahr, Peter ; Hoffmann, Saskia ; Tollenaere, Maxim A X ; Ho, Teresa ; Toledo Lazaro, Luis Ignacio ; Mann, Matthias ; Bekker-Jensen, Simon ; Räschle, Markus ; Mailand, Niels. / Activation of the ATR kinase by the RPA-binding protein ETAA1. In: Nature Cell Biology. 2016 ; Vol. 18, No. 11. pp. 1196–1207.

Bibtex

@article{d61c951a54374105b4023faa7e81fa85,
title = "Activation of the ATR kinase by the RPA-binding protein ETAA1",
abstract = "Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults. Mechanistically, this requires a conserved domain in ETAA1 that potently and directly stimulates ATR kinase activity independently of TopBP1. Simultaneous loss of ETAA1 and TopBP1 gives rise to synthetic lethality characterized by massive genome instability and abrogation of ATR-dependent signalling. Our findings demonstrate that parallel TopBP1- and ETAA1-mediated pathways underlie ATR activation and that their combined action is essential for coping with replication stress.",
author = "Peter Haahr and Saskia Hoffmann and Tollenaere, {Maxim A X} and Teresa Ho and {Toledo Lazaro}, {Luis Ignacio} and Matthias Mann and Simon Bekker-Jensen and Markus R{\"a}schle and Niels Mailand",
year = "2016",
month = nov,
doi = "10.1038/ncb3422",
language = "English",
volume = "18",
pages = "1196–1207",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "nature publishing group",
number = "11",

}

RIS

TY - JOUR

T1 - Activation of the ATR kinase by the RPA-binding protein ETAA1

AU - Haahr, Peter

AU - Hoffmann, Saskia

AU - Tollenaere, Maxim A X

AU - Ho, Teresa

AU - Toledo Lazaro, Luis Ignacio

AU - Mann, Matthias

AU - Bekker-Jensen, Simon

AU - Räschle, Markus

AU - Mailand, Niels

PY - 2016/11

Y1 - 2016/11

N2 - Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults. Mechanistically, this requires a conserved domain in ETAA1 that potently and directly stimulates ATR kinase activity independently of TopBP1. Simultaneous loss of ETAA1 and TopBP1 gives rise to synthetic lethality characterized by massive genome instability and abrogation of ATR-dependent signalling. Our findings demonstrate that parallel TopBP1- and ETAA1-mediated pathways underlie ATR activation and that their combined action is essential for coping with replication stress.

AB - Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults. Mechanistically, this requires a conserved domain in ETAA1 that potently and directly stimulates ATR kinase activity independently of TopBP1. Simultaneous loss of ETAA1 and TopBP1 gives rise to synthetic lethality characterized by massive genome instability and abrogation of ATR-dependent signalling. Our findings demonstrate that parallel TopBP1- and ETAA1-mediated pathways underlie ATR activation and that their combined action is essential for coping with replication stress.

U2 - 10.1038/ncb3422

DO - 10.1038/ncb3422

M3 - Journal article

C2 - 27723717

VL - 18

SP - 1196

EP - 1207

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 11

ER -

ID: 167176588