Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response

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Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response. / Beli, Petra; Lukashchuk, Natalia; Wagner, Sebastian A; Weinert, Brian T; Olsen, Jesper V; Baskcomb, Linda; Mann, Matthias; Jackson, Stephen P; Choudhary, Chuna Ram.

In: Molecular Cell, Vol. 46, No. 2, 2012, p. 212-25.

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

Harvard

Beli, P, Lukashchuk, N, Wagner, SA, Weinert, BT, Olsen, JV, Baskcomb, L, Mann, M, Jackson, SP & Choudhary, CR 2012, 'Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response', Molecular Cell, vol. 46, no. 2, pp. 212-25. https://doi.org/10.1016/j.molcel.2012.01.026

APA

Beli, P., Lukashchuk, N., Wagner, S. A., Weinert, B. T., Olsen, J. V., Baskcomb, L., Mann, M., Jackson, S. P., & Choudhary, C. R. (2012). Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response. Molecular Cell, 46(2), 212-25. https://doi.org/10.1016/j.molcel.2012.01.026

Vancouver

Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L et al. Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response. Molecular Cell. 2012;46(2):212-25. https://doi.org/10.1016/j.molcel.2012.01.026

Author

Beli, Petra ; Lukashchuk, Natalia ; Wagner, Sebastian A ; Weinert, Brian T ; Olsen, Jesper V ; Baskcomb, Linda ; Mann, Matthias ; Jackson, Stephen P ; Choudhary, Chuna Ram. / Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response. In: Molecular Cell. 2012 ; Vol. 46, No. 2. pp. 212-25.

Bibtex

@article{36b3055221a84c9aae0b7d3c44735890,
title = "Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response",
abstract = "The regulatory networks of the DNA damage response (DDR) encompass many proteins and posttranslational modifications. Here, we use mass spectrometry-based proteomics to analyze the systems-wide response to DNA damage by parallel quantification of the DDR-regulated phosphoproteome, acetylome, and proteome. We show that phosphorylation-dependent signaling networks are regulated more strongly compared to acetylation. Among the phosphorylated proteins identified are many putative substrates of DNA-PK, ATM, and ATR kinases, but a majority of phosphorylated proteins do not share the ATM/ATR/DNA-PK target consensus motif, suggesting an important role of downstream kinases in amplifying DDR signals. We show that the splicing-regulator phosphatase PPM1G is recruited to sites of DNA damage, while the splicing-associated protein THRAP3 is excluded from these regions. Moreover, THRAP3 depletion causes cellular hypersensitivity to DNA-damaging agents. Collectively, these data broaden our knowledge of DNA damage signaling networks and highlight an important link between RNA metabolism and DNA repair.",
keywords = "Cell Line, Tumor, DNA Damage, DNA Repair, DNA-Binding Proteins, HeLa Cells, Humans, Phosphoprotein Phosphatases, Phosphorylation, Proteomics, Signal Transduction, Transcription Factors, Tumor Necrosis Factor-alpha",
author = "Petra Beli and Natalia Lukashchuk and Wagner, {Sebastian A} and Weinert, {Brian T} and Olsen, {Jesper V} and Linda Baskcomb and Matthias Mann and Jackson, {Stephen P} and Choudhary, {Chuna Ram}",
note = "Copyright {\textcopyright} 2012 Elsevier Inc. All rights reserved.",
year = "2012",
doi = "10.1016/j.molcel.2012.01.026",
language = "English",
volume = "46",
pages = "212--25",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response

AU - Beli, Petra

AU - Lukashchuk, Natalia

AU - Wagner, Sebastian A

AU - Weinert, Brian T

AU - Olsen, Jesper V

AU - Baskcomb, Linda

AU - Mann, Matthias

AU - Jackson, Stephen P

AU - Choudhary, Chuna Ram

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012

Y1 - 2012

N2 - The regulatory networks of the DNA damage response (DDR) encompass many proteins and posttranslational modifications. Here, we use mass spectrometry-based proteomics to analyze the systems-wide response to DNA damage by parallel quantification of the DDR-regulated phosphoproteome, acetylome, and proteome. We show that phosphorylation-dependent signaling networks are regulated more strongly compared to acetylation. Among the phosphorylated proteins identified are many putative substrates of DNA-PK, ATM, and ATR kinases, but a majority of phosphorylated proteins do not share the ATM/ATR/DNA-PK target consensus motif, suggesting an important role of downstream kinases in amplifying DDR signals. We show that the splicing-regulator phosphatase PPM1G is recruited to sites of DNA damage, while the splicing-associated protein THRAP3 is excluded from these regions. Moreover, THRAP3 depletion causes cellular hypersensitivity to DNA-damaging agents. Collectively, these data broaden our knowledge of DNA damage signaling networks and highlight an important link between RNA metabolism and DNA repair.

AB - The regulatory networks of the DNA damage response (DDR) encompass many proteins and posttranslational modifications. Here, we use mass spectrometry-based proteomics to analyze the systems-wide response to DNA damage by parallel quantification of the DDR-regulated phosphoproteome, acetylome, and proteome. We show that phosphorylation-dependent signaling networks are regulated more strongly compared to acetylation. Among the phosphorylated proteins identified are many putative substrates of DNA-PK, ATM, and ATR kinases, but a majority of phosphorylated proteins do not share the ATM/ATR/DNA-PK target consensus motif, suggesting an important role of downstream kinases in amplifying DDR signals. We show that the splicing-regulator phosphatase PPM1G is recruited to sites of DNA damage, while the splicing-associated protein THRAP3 is excluded from these regions. Moreover, THRAP3 depletion causes cellular hypersensitivity to DNA-damaging agents. Collectively, these data broaden our knowledge of DNA damage signaling networks and highlight an important link between RNA metabolism and DNA repair.

KW - Cell Line, Tumor

KW - DNA Damage

KW - DNA Repair

KW - DNA-Binding Proteins

KW - HeLa Cells

KW - Humans

KW - Phosphoprotein Phosphatases

KW - Phosphorylation

KW - Proteomics

KW - Signal Transduction

KW - Transcription Factors

KW - Tumor Necrosis Factor-alpha

U2 - 10.1016/j.molcel.2012.01.026

DO - 10.1016/j.molcel.2012.01.026

M3 - Journal article

C2 - 22424773

VL - 46

SP - 212

EP - 225

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 2

ER -

ID: 40288839