Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks

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Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks. / Poulsen, Maria; Lukas, Claudia; Lukas, Jiri; Bekker-Jensen, Simon; Mailand, Niels.

In: Journal of Cell Biology, Vol. 197, No. 2, 2012, p. 189-99.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Poulsen, M, Lukas, C, Lukas, J, Bekker-Jensen, S & Mailand, N 2012, 'Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks', Journal of Cell Biology, vol. 197, no. 2, pp. 189-99. https://doi.org/10.1083/jcb.201109100

APA

Poulsen, M., Lukas, C., Lukas, J., Bekker-Jensen, S., & Mailand, N. (2012). Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks. Journal of Cell Biology, 197(2), 189-99. https://doi.org/10.1083/jcb.201109100

Vancouver

Poulsen M, Lukas C, Lukas J, Bekker-Jensen S, Mailand N. Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks. Journal of Cell Biology. 2012;197(2):189-99. https://doi.org/10.1083/jcb.201109100

Author

Poulsen, Maria ; Lukas, Claudia ; Lukas, Jiri ; Bekker-Jensen, Simon ; Mailand, Niels. / Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks. In: Journal of Cell Biology. 2012 ; Vol. 197, No. 2. pp. 189-99.

Bibtex

@article{fb65bc3bbbb14f55b493e04b9b0bbfad,
title = "Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks",
abstract = "Nonproteolytic ubiquitylation of chromatin surrounding deoxyribonucleic acid double-strand breaks (DSBs), mediated by the RNF8/RNF168 ubiquitin ligases, plays a key role in recruiting repair factors, including 53BP1 and BRCA1, to reestablish genome integrity. In this paper, we show that human RNF169, an uncharacterized E3 ubiquitin ligase paralogous to RNF168, accumulated in DSB repair foci through recognition of RNF168-catalyzed ubiquitylation products by its motif interacting with ubiquitin domain. Unexpectedly, RNF169 was dispensable for chromatin ubiquitylation and ubiquitin-dependent accumulation of repair factors at DSB sites. Instead, RNF169 functionally competed with 53BP1 and RAP80-BRCA1 for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of their recruitment to DSB sites. By delaying accumulation of 53BP1 and RAP80 at damaged chromatin, RNF169 stimulated homologous recombination and restrained nonhomologous end joining, affecting cell survival after DSB infliction. Our results show that RNF169 functions in a noncanonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization.",
keywords = "BRCA1 Protein, Carrier Proteins, Cell Line, Tumor, Cell Survival, Chromatin, DNA, DNA Breaks, Double-Stranded, DNA End-Joining Repair, DNA-Binding Proteins, HEK293 Cells, HeLa Cells, Homologous Recombination, Humans, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, RNA Interference, RNA, Small Interfering, Ubiquitin, Ubiquitin-Protein Ligases, Ubiquitination, Zinc Fingers",
author = "Maria Poulsen and Claudia Lukas and Jiri Lukas and Simon Bekker-Jensen and Niels Mailand",
year = "2012",
doi = "10.1083/jcb.201109100",
language = "English",
volume = "197",
pages = "189--99",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks

AU - Poulsen, Maria

AU - Lukas, Claudia

AU - Lukas, Jiri

AU - Bekker-Jensen, Simon

AU - Mailand, Niels

PY - 2012

Y1 - 2012

N2 - Nonproteolytic ubiquitylation of chromatin surrounding deoxyribonucleic acid double-strand breaks (DSBs), mediated by the RNF8/RNF168 ubiquitin ligases, plays a key role in recruiting repair factors, including 53BP1 and BRCA1, to reestablish genome integrity. In this paper, we show that human RNF169, an uncharacterized E3 ubiquitin ligase paralogous to RNF168, accumulated in DSB repair foci through recognition of RNF168-catalyzed ubiquitylation products by its motif interacting with ubiquitin domain. Unexpectedly, RNF169 was dispensable for chromatin ubiquitylation and ubiquitin-dependent accumulation of repair factors at DSB sites. Instead, RNF169 functionally competed with 53BP1 and RAP80-BRCA1 for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of their recruitment to DSB sites. By delaying accumulation of 53BP1 and RAP80 at damaged chromatin, RNF169 stimulated homologous recombination and restrained nonhomologous end joining, affecting cell survival after DSB infliction. Our results show that RNF169 functions in a noncanonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization.

AB - Nonproteolytic ubiquitylation of chromatin surrounding deoxyribonucleic acid double-strand breaks (DSBs), mediated by the RNF8/RNF168 ubiquitin ligases, plays a key role in recruiting repair factors, including 53BP1 and BRCA1, to reestablish genome integrity. In this paper, we show that human RNF169, an uncharacterized E3 ubiquitin ligase paralogous to RNF168, accumulated in DSB repair foci through recognition of RNF168-catalyzed ubiquitylation products by its motif interacting with ubiquitin domain. Unexpectedly, RNF169 was dispensable for chromatin ubiquitylation and ubiquitin-dependent accumulation of repair factors at DSB sites. Instead, RNF169 functionally competed with 53BP1 and RAP80-BRCA1 for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of their recruitment to DSB sites. By delaying accumulation of 53BP1 and RAP80 at damaged chromatin, RNF169 stimulated homologous recombination and restrained nonhomologous end joining, affecting cell survival after DSB infliction. Our results show that RNF169 functions in a noncanonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization.

KW - BRCA1 Protein

KW - Carrier Proteins

KW - Cell Line, Tumor

KW - Cell Survival

KW - Chromatin

KW - DNA

KW - DNA Breaks, Double-Stranded

KW - DNA End-Joining Repair

KW - DNA-Binding Proteins

KW - HEK293 Cells

KW - HeLa Cells

KW - Homologous Recombination

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Nuclear Proteins

KW - RNA Interference

KW - RNA, Small Interfering

KW - Ubiquitin

KW - Ubiquitin-Protein Ligases

KW - Ubiquitination

KW - Zinc Fingers

U2 - 10.1083/jcb.201109100

DO - 10.1083/jcb.201109100

M3 - Journal article

C2 - 22492721

VL - 197

SP - 189

EP - 199

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 2

ER -

ID: 40289827