Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination

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

Standard

Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination. / Nakamura, Kyosuke; Kustatscher, Georg; Alabert, Constance; Hödl, Martina; Forne, Ignasi; Völker-Albert, Moritz; Satpathy, Shankha; Beyer, Tracey E; Mailand, Niels; Choudhary, Chunaram; Imhof, Axel; Rappsilber, Juri; Groth, Anja.

In: Molecular Cell, Vol. 81, No. 3, 2021.

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

Harvard

Nakamura, K, Kustatscher, G, Alabert, C, Hödl, M, Forne, I, Völker-Albert, M, Satpathy, S, Beyer, TE, Mailand, N, Choudhary, C, Imhof, A, Rappsilber, J & Groth, A 2021, 'Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination', Molecular Cell, vol. 81, no. 3. https://doi.org/10.1016/j.molcel.2020.12.025

APA

Nakamura, K., Kustatscher, G., Alabert, C., Hödl, M., Forne, I., Völker-Albert, M., Satpathy, S., Beyer, T. E., Mailand, N., Choudhary, C., Imhof, A., Rappsilber, J., & Groth, A. (2021). Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination. Molecular Cell, 81(3). https://doi.org/10.1016/j.molcel.2020.12.025

Vancouver

Nakamura K, Kustatscher G, Alabert C, Hödl M, Forne I, Völker-Albert M et al. Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination. Molecular Cell. 2021;81(3). https://doi.org/10.1016/j.molcel.2020.12.025

Author

Nakamura, Kyosuke ; Kustatscher, Georg ; Alabert, Constance ; Hödl, Martina ; Forne, Ignasi ; Völker-Albert, Moritz ; Satpathy, Shankha ; Beyer, Tracey E ; Mailand, Niels ; Choudhary, Chunaram ; Imhof, Axel ; Rappsilber, Juri ; Groth, Anja. / Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination. In: Molecular Cell. 2021 ; Vol. 81, No. 3.

Bibtex

@article{7bb1ec84ef29478ea0b0932db9390f38,
title = "Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination",
abstract = "Cells have evolved an elaborate DNA repair network to ensure complete and accurate DNA replication. Defects in these repair machineries can fuel genome instability and drive carcinogenesis while creating vulnerabilities that may be exploited in therapy. Here, we use nascent chromatin capture (NCC) proteomics to characterize the repair of replication-associated DNA double-strand breaks (DSBs) triggered by topoisomerase 1 (TOP1) inhibitors. We reveal profound changes in the fork proteome, including the chromatin environment and nuclear membrane interactions, and identify three classes of repair factors according to their enrichment at broken and/or stalled forks. ATM inhibition dramatically rewired the broken fork proteome, revealing that ataxia telangiectasia mutated (ATM) signalling stimulates DNA end resection, recruits PLK1, and concomitantly suppresses the canonical DSB ubiquitination response by preventing accumulation of RNF168 and BRCA1-A. This work and collection of replication fork proteomes provide a new framework to understand how cells orchestrate homologous recombination repair of replication-associated DSBs.",
author = "Kyosuke Nakamura and Georg Kustatscher and Constance Alabert and Martina H{\"o}dl and Ignasi Forne and Moritz V{\"o}lker-Albert and Shankha Satpathy and Beyer, {Tracey E} and Niels Mailand and Chunaram Choudhary and Axel Imhof and Juri Rappsilber and Anja Groth",
year = "2021",
doi = "10.1016/j.molcel.2020.12.025",
language = "English",
volume = "81",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination

AU - Nakamura, Kyosuke

AU - Kustatscher, Georg

AU - Alabert, Constance

AU - Hödl, Martina

AU - Forne, Ignasi

AU - Völker-Albert, Moritz

AU - Satpathy, Shankha

AU - Beyer, Tracey E

AU - Mailand, Niels

AU - Choudhary, Chunaram

AU - Imhof, Axel

AU - Rappsilber, Juri

AU - Groth, Anja

PY - 2021

Y1 - 2021

N2 - Cells have evolved an elaborate DNA repair network to ensure complete and accurate DNA replication. Defects in these repair machineries can fuel genome instability and drive carcinogenesis while creating vulnerabilities that may be exploited in therapy. Here, we use nascent chromatin capture (NCC) proteomics to characterize the repair of replication-associated DNA double-strand breaks (DSBs) triggered by topoisomerase 1 (TOP1) inhibitors. We reveal profound changes in the fork proteome, including the chromatin environment and nuclear membrane interactions, and identify three classes of repair factors according to their enrichment at broken and/or stalled forks. ATM inhibition dramatically rewired the broken fork proteome, revealing that ataxia telangiectasia mutated (ATM) signalling stimulates DNA end resection, recruits PLK1, and concomitantly suppresses the canonical DSB ubiquitination response by preventing accumulation of RNF168 and BRCA1-A. This work and collection of replication fork proteomes provide a new framework to understand how cells orchestrate homologous recombination repair of replication-associated DSBs.

AB - Cells have evolved an elaborate DNA repair network to ensure complete and accurate DNA replication. Defects in these repair machineries can fuel genome instability and drive carcinogenesis while creating vulnerabilities that may be exploited in therapy. Here, we use nascent chromatin capture (NCC) proteomics to characterize the repair of replication-associated DNA double-strand breaks (DSBs) triggered by topoisomerase 1 (TOP1) inhibitors. We reveal profound changes in the fork proteome, including the chromatin environment and nuclear membrane interactions, and identify three classes of repair factors according to their enrichment at broken and/or stalled forks. ATM inhibition dramatically rewired the broken fork proteome, revealing that ataxia telangiectasia mutated (ATM) signalling stimulates DNA end resection, recruits PLK1, and concomitantly suppresses the canonical DSB ubiquitination response by preventing accumulation of RNF168 and BRCA1-A. This work and collection of replication fork proteomes provide a new framework to understand how cells orchestrate homologous recombination repair of replication-associated DSBs.

U2 - 10.1016/j.molcel.2020.12.025

DO - 10.1016/j.molcel.2020.12.025

M3 - Journal article

C2 - 33450211

VL - 81

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 3

ER -

ID: 255561231