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Cited by 659

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

RNF168 Ubiquitinates K13-15 on H2A/H2AX to Drive DNA Damage Signaling

Open access
Mattiroli, Francesca, Vissers, Joseph H.A., van Dijk, Willem J., Ikpa, Pauline, Citterio, Elisabetta, Vermeulen, Wim, Marteijn, Jurgen A., Sixma, Titia K.·2012·Cell

Abstract

Ubiquitin-dependent signaling during the DNA damage response (DDR) to double-strand breaks (DSBs) is initiated by two E3 ligases, RNF8 and RNF168, targeting histone H2A and H2AX. RNF8 is the first ligase recruited to the damage site, and RNF168 follows RNF8-dependent ubiquitination. This suggests that RNF8 initiates H2A/H2AX ubiquitination with K63-linked ubiquitin chains and RNF168 extends them. Here, we show that RNF8 is inactive toward nucleosomal H2A, whereas RNF168 catalyzes the monoubiquitination of the histones specifically on K13-15. Structure-based mutagenesis of RNF8 and RNF168 RING domains shows that a charged residue determines whether nucleosomal proteins are recognized. We find that K63 ubiquitin chains are conjugated to RNF168-dependent H2A/H2AX monoubiquitination at K13-15 and not on K118-119. Using a mutant of RNF168 unable to target histones but still catalyzing ubiquitin chains at DSBs, we show that ubiquitin chains per se are insufficient for signaling, but RNF168 target ubiquitination is required for DDR.

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Crossref · 10.1016/j.cell.2012.08.005

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Metadata

Authors
Mattiroli, F., Vissers, J. H. A., van Dijk, W. J., Ikpa, P., Citterio, E., Vermeulen, W., Marteijn, J. A., & Sixma, T. K.
Venue
Cell
Publisher
Elsevier BV
Published
2012-09
Volume
150
Issue
6
Pages
1182-1195
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2084377803
Cited by
659
References
6
FWCI
14.99
Type
journal article
Language
en
Open access
bronze

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