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.
I: Molecular Cell, Bind 46, Nr. 2, 2012, s. 212-25.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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