RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins

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

Standard

RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. / Doil, Carsten; Mailand, Niels; Bekker-Jensen, Simon; Menard, Patrice; Larsen, Dorthe Helena; Pepperkok, Rainer; Ellenberg, Jan; Panier, Stephanie; Durocher, Daniel; Bartek, Jiri; Lukas, Jiri; Lukas, Claudia.

In: Cell, Vol. 136, No. 3, 2009, p. 435-46.

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

Harvard

Doil, C, Mailand, N, Bekker-Jensen, S, Menard, P, Larsen, DH, Pepperkok, R, Ellenberg, J, Panier, S, Durocher, D, Bartek, J, Lukas, J & Lukas, C 2009, 'RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins', Cell, vol. 136, no. 3, pp. 435-46. https://doi.org/10.1016/j.cell.2008.12.041

APA

Doil, C., Mailand, N., Bekker-Jensen, S., Menard, P., Larsen, D. H., Pepperkok, R., Ellenberg, J., Panier, S., Durocher, D., Bartek, J., Lukas, J., & Lukas, C. (2009). RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell, 136(3), 435-46. https://doi.org/10.1016/j.cell.2008.12.041

Vancouver

Doil C, Mailand N, Bekker-Jensen S, Menard P, Larsen DH, Pepperkok R et al. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell. 2009;136(3):435-46. https://doi.org/10.1016/j.cell.2008.12.041

Author

Doil, Carsten ; Mailand, Niels ; Bekker-Jensen, Simon ; Menard, Patrice ; Larsen, Dorthe Helena ; Pepperkok, Rainer ; Ellenberg, Jan ; Panier, Stephanie ; Durocher, Daniel ; Bartek, Jiri ; Lukas, Jiri ; Lukas, Claudia. / RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. In: Cell. 2009 ; Vol. 136, No. 3. pp. 435-46.

Bibtex

@article{2a7e8e90333311df8ed1000ea68e967b,
title = "RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins",
abstract = "DNA double-strand breaks (DSBs) not only interrupt the genetic information, but also disrupt the chromatin structure, and both impairments require repair mechanisms to ensure genome integrity. We showed previously that RNF8-mediated chromatin ubiquitylation protects genome integrity by promoting the accumulation of repair factors at DSBs. Here, we provide evidence that, while RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment. We identified RNF168 as a novel chromatin-associated ubiquitin ligase with an ability to bind ubiquitin. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1. Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance.",
author = "Carsten Doil and Niels Mailand and Simon Bekker-Jensen and Patrice Menard and Larsen, {Dorthe Helena} and Rainer Pepperkok and Jan Ellenberg and Stephanie Panier and Daniel Durocher and Jiri Bartek and Jiri Lukas and Claudia Lukas",
note = "Keywords: Cell Line; Chromosomes; DNA Breaks, Double-Stranded; DNA Repair; DNA-Binding Proteins; Gene Knockdown Techniques; Histones; Humans; Intracellular Signaling Peptides and Proteins; Protein Structure, Tertiary; Ubiquitin; Ubiquitin-Protein Ligases",
year = "2009",
doi = "10.1016/j.cell.2008.12.041",
language = "English",
volume = "136",
pages = "435--46",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins

AU - Doil, Carsten

AU - Mailand, Niels

AU - Bekker-Jensen, Simon

AU - Menard, Patrice

AU - Larsen, Dorthe Helena

AU - Pepperkok, Rainer

AU - Ellenberg, Jan

AU - Panier, Stephanie

AU - Durocher, Daniel

AU - Bartek, Jiri

AU - Lukas, Jiri

AU - Lukas, Claudia

N1 - Keywords: Cell Line; Chromosomes; DNA Breaks, Double-Stranded; DNA Repair; DNA-Binding Proteins; Gene Knockdown Techniques; Histones; Humans; Intracellular Signaling Peptides and Proteins; Protein Structure, Tertiary; Ubiquitin; Ubiquitin-Protein Ligases

PY - 2009

Y1 - 2009

N2 - DNA double-strand breaks (DSBs) not only interrupt the genetic information, but also disrupt the chromatin structure, and both impairments require repair mechanisms to ensure genome integrity. We showed previously that RNF8-mediated chromatin ubiquitylation protects genome integrity by promoting the accumulation of repair factors at DSBs. Here, we provide evidence that, while RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment. We identified RNF168 as a novel chromatin-associated ubiquitin ligase with an ability to bind ubiquitin. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1. Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance.

AB - DNA double-strand breaks (DSBs) not only interrupt the genetic information, but also disrupt the chromatin structure, and both impairments require repair mechanisms to ensure genome integrity. We showed previously that RNF8-mediated chromatin ubiquitylation protects genome integrity by promoting the accumulation of repair factors at DSBs. Here, we provide evidence that, while RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment. We identified RNF168 as a novel chromatin-associated ubiquitin ligase with an ability to bind ubiquitin. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1. Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance.

U2 - 10.1016/j.cell.2008.12.041

DO - 10.1016/j.cell.2008.12.041

M3 - Journal article

C2 - 19203579

VL - 136

SP - 435

EP - 446

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

ER -

ID: 18697996