Journal article
RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage.
- Gatti M Department of Pharmaceutical Sciences, University of Piemonte Orientale, via Bovio 2, 28100 Novara, Italy.
- Pinato S Department of Pharmaceutical Sciences, University of Piemonte Orientale, via Bovio 2, 28100 Novara, Italy.
- Maiolica A Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zurich (ETHZ), 8093 Zurich, Switzerland.
- Rocchio F Department of Pharmaceutical Sciences, University of Piemonte Orientale, via Bovio 2, 28100 Novara, Italy.
- Prato MG Department of Pharmaceutical Sciences, University of Piemonte Orientale, via Bovio 2, 28100 Novara, Italy.
- Aebersold R Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule Zurich (ETHZ), 8093 Zurich, Switzerland; Faculty of Science, University of Zurich, 8057 Zurich, Switzerland.
- Penengo L Department of Pharmaceutical Sciences, University of Piemonte Orientale, via Bovio 2, 28100 Novara, Italy; Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, 8057 Zurich, Switzerland. Electronic address: lorenza.penengo@uzh.ch.
- 2015-01-13
Published in:
- Cell reports. - 2015
Amino Acid Sequence
BRCA1 Protein
Cell Line, Tumor
Chromatin
DNA Damage
DNA Repair
HEK293 Cells
Histones
Humans
Intracellular Signaling Peptides and Proteins
Molecular Sequence Data
RNA Interference
RNA, Small Interfering
Tumor Suppressor p53-Binding Protein 1
Ubiquitin
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligases
Ubiquitination
English
Ubiquitination regulates numerous cellular processes by generating a versatile communication system based on eight structurally and functionally different chains linked through distinct residues. Except for K48 and K63, the biological relevance of different linkages is largely unclear. Here, we show that RNF168 ubiquitin ligase promotes noncanonical K27-linked ubiquitination both in vivo and in vitro. We demonstrate that residue K27 of ubiquitin (UbK27) is required for RNF168-dependent chromatin ubiquitination, by targeting histones H2A/H2A.X, and that it is the major ubiquitin-based modification marking chromatin upon DNA damage. Indeed, UbK27 is strictly required for the proper activation of the DNA damage response (DDR) and is directly recognized by crucial DDR mediators, namely 53BP1, Rap80, RNF168, and RNF169. Mutation of UbK27 has dramatic consequences on DDR activation, preventing the recruitment of 53BP1 and BRCA1 to DDR foci. Similarly to the DDR, atypical ubiquitin chains could play unanticipated roles in other crucial ubiquitin-mediated biological processes.
- Language
-
- English
- Open access status
- gold
- Identifiers
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- DOI 10.1016/j.celrep.2014.12.021
- PMID 25578731
- Persistent URL
- https://sonar.ch/global/documents/52305
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