Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass

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

Standard

Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. / Povlsen, Lou K; Beli, Petra; Wagner, Sebastian A; Poulsen, Sara L; Sylvestersen, Kathrine B; Poulsen, Jon Wriedt; Nielsen, Michael L; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chuna Ram.

In: Nature Cell Biology, Vol. 14, No. 10, 10.2012, p. 1089-98.

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

Harvard

Povlsen, LK, Beli, P, Wagner, SA, Poulsen, SL, Sylvestersen, KB, Poulsen, JW, Nielsen, ML, Bekker-Jensen, S, Mailand, N & Choudhary, CR 2012, 'Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass', Nature Cell Biology, vol. 14, no. 10, pp. 1089-98. https://doi.org/10.1038/ncb2579

APA

Povlsen, L. K., Beli, P., Wagner, S. A., Poulsen, S. L., Sylvestersen, K. B., Poulsen, J. W., Nielsen, M. L., Bekker-Jensen, S., Mailand, N., & Choudhary, C. R. (2012). Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Nature Cell Biology, 14(10), 1089-98. https://doi.org/10.1038/ncb2579

Vancouver

Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW et al. Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. Nature Cell Biology. 2012 Oct;14(10):1089-98. https://doi.org/10.1038/ncb2579

Author

Povlsen, Lou K ; Beli, Petra ; Wagner, Sebastian A ; Poulsen, Sara L ; Sylvestersen, Kathrine B ; Poulsen, Jon Wriedt ; Nielsen, Michael L ; Bekker-Jensen, Simon ; Mailand, Niels ; Choudhary, Chuna Ram. / Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass. In: Nature Cell Biology. 2012 ; Vol. 14, No. 10. pp. 1089-98.

Bibtex

@article{d257b8e1794f4398bed43dda7ea6878a,
title = "Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass",
abstract = "Protein ubiquitylation has emerged as a key regulatory mechanism in DNA-damage signalling and repair pathways. We report a proteome-wide, site-specific survey of ubiquitylation changes after ultraviolet irradiation, identifying numerous upregulated and downregulated ubiquitylation sites on known components of DNA-damage signalling, as well as on proteins not previously implicated in this process. Our results uncover a critical role for PCNA-associated factor PAF15 (p15(PAF)/KIAA0101) ubiquitylation during DNA replication. During unperturbed S phase, chromatin-associated PAF15 is modified by double mono-ubiquitylation of Lys 15 and 24 templated through PCNA binding. Replication blocks trigger rapid, proteasome-dependent removal of Lys 15/24-ubiquitylated PAF15 from PCNA, facilitating bypass of replication-fork-blocking lesions by allowing recruitment of translesion DNA synthesis polymerase polη to mono-ubiquitylated PCNA at stalled replisomes. Our findings demonstrate widespread involvement of ubiquitin signalling in genotoxic-stress responses and identify a critical function for dynamic PAF15 ubiquitylation in safeguarding genome integrity when DNA replication is challenged.",
keywords = "Carrier Proteins, Cell Line, DNA Damage, DNA Repair, DNA Replication, DNA-Directed DNA Polymerase, Humans, Lysine, Proteasome Endopeptidase Complex, S Phase, Signal Transduction, Ubiquitination, Ultraviolet Rays",
author = "Povlsen, {Lou K} and Petra Beli and Wagner, {Sebastian A} and Poulsen, {Sara L} and Sylvestersen, {Kathrine B} and Poulsen, {Jon Wriedt} and Nielsen, {Michael L} and Simon Bekker-Jensen and Niels Mailand and Choudhary, {Chuna Ram}",
year = "2012",
month = oct,
doi = "10.1038/ncb2579",
language = "English",
volume = "14",
pages = "1089--98",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "nature publishing group",
number = "10",

}

RIS

TY - JOUR

T1 - Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass

AU - Povlsen, Lou K

AU - Beli, Petra

AU - Wagner, Sebastian A

AU - Poulsen, Sara L

AU - Sylvestersen, Kathrine B

AU - Poulsen, Jon Wriedt

AU - Nielsen, Michael L

AU - Bekker-Jensen, Simon

AU - Mailand, Niels

AU - Choudhary, Chuna Ram

PY - 2012/10

Y1 - 2012/10

N2 - Protein ubiquitylation has emerged as a key regulatory mechanism in DNA-damage signalling and repair pathways. We report a proteome-wide, site-specific survey of ubiquitylation changes after ultraviolet irradiation, identifying numerous upregulated and downregulated ubiquitylation sites on known components of DNA-damage signalling, as well as on proteins not previously implicated in this process. Our results uncover a critical role for PCNA-associated factor PAF15 (p15(PAF)/KIAA0101) ubiquitylation during DNA replication. During unperturbed S phase, chromatin-associated PAF15 is modified by double mono-ubiquitylation of Lys 15 and 24 templated through PCNA binding. Replication blocks trigger rapid, proteasome-dependent removal of Lys 15/24-ubiquitylated PAF15 from PCNA, facilitating bypass of replication-fork-blocking lesions by allowing recruitment of translesion DNA synthesis polymerase polη to mono-ubiquitylated PCNA at stalled replisomes. Our findings demonstrate widespread involvement of ubiquitin signalling in genotoxic-stress responses and identify a critical function for dynamic PAF15 ubiquitylation in safeguarding genome integrity when DNA replication is challenged.

AB - Protein ubiquitylation has emerged as a key regulatory mechanism in DNA-damage signalling and repair pathways. We report a proteome-wide, site-specific survey of ubiquitylation changes after ultraviolet irradiation, identifying numerous upregulated and downregulated ubiquitylation sites on known components of DNA-damage signalling, as well as on proteins not previously implicated in this process. Our results uncover a critical role for PCNA-associated factor PAF15 (p15(PAF)/KIAA0101) ubiquitylation during DNA replication. During unperturbed S phase, chromatin-associated PAF15 is modified by double mono-ubiquitylation of Lys 15 and 24 templated through PCNA binding. Replication blocks trigger rapid, proteasome-dependent removal of Lys 15/24-ubiquitylated PAF15 from PCNA, facilitating bypass of replication-fork-blocking lesions by allowing recruitment of translesion DNA synthesis polymerase polη to mono-ubiquitylated PCNA at stalled replisomes. Our findings demonstrate widespread involvement of ubiquitin signalling in genotoxic-stress responses and identify a critical function for dynamic PAF15 ubiquitylation in safeguarding genome integrity when DNA replication is challenged.

KW - Carrier Proteins

KW - Cell Line

KW - DNA Damage

KW - DNA Repair

KW - DNA Replication

KW - DNA-Directed DNA Polymerase

KW - Humans

KW - Lysine

KW - Proteasome Endopeptidase Complex

KW - S Phase

KW - Signal Transduction

KW - Ubiquitination

KW - Ultraviolet Rays

U2 - 10.1038/ncb2579

DO - 10.1038/ncb2579

M3 - Journal article

C2 - 23000965

VL - 14

SP - 1089

EP - 1098

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 10

ER -

ID: 46282763