Reactome | RNF168 binds DNA DSBs

RNF168 binds DNA DSBs

Stable Identifier

R-HSA-5682863

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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The recruitment of RNF168, an E3 ubiquitin ligase, to DNA double-strand breaks (DSBs) is facilitated by the interaction of RNF168 with the UBE2N:UBE2V2 (UBC13:MMS2) complex, which serves as the E2 ubiquitin ligase for both RNF8 and RNF168. In addition, because the two RNF168 ubiquitin interaction motifs (UIMs) are needed for the accumulation of RNF168 at DSBs, the initial ubiquitination of H2AFX (H2AX) histones by RNF8 is likely involved in RNF168 recruitment to DSBs. Inactivating mutations in both RNF168 alleles are responsible for the RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features and learning difficulties) syndrome (Stewart et al. 2009, Doil et al. 2009, Bekker-Jensen et al. 2010, Campbell et al. 2012, Mattiroli et al. 2012).

Literature References

PubMed ID	Title	Journal	Year
20023648	HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes Lukas, J, Gromova, I, Rendtlew Danielsen, J, Bartek, J, Nerstedt, A, Lukas, C, Fugger, K, Bekker-Jensen, S, Mailand, N	Nat. Cell Biol.	2010
22589545	Molecular insights into the function of RING finger (RNF)-containing proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation Campbell, SJ, Neculai, D, Leung, CC, Glover, JN, Dhe-Paganon, S, Hodge, CD, Edwards, RA	J. Biol. Chem.	2012
19203578	The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage Townsend, K, Al-Hakim, AK, Stankovic, T, Taylor, AM, Byrd, PJ, Stewart, GS, Pelletier, L, Oldreive, C, Olivarius, S, Taubenheim, N, Durocher, D, Panier, S, Mendez, M, Wildenhain, J, Nakada, S, Kolas, NK, Miller, ES, Tagliaferro, A, Durandy, A, Ylanko, J	Cell	2009
22980979	RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling Sixma, TK, Marteijn, JA, Vissers, JH, Citterio, E, Ikpa, P, Mattiroli, F, van Dijk, WJ, Vermeulen, W	Cell	2012
19203579	RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins Durocher, D, Panier, S, Doil, C, Larsen, DH, Lukas, J, Menard, P, Bartek, J, Pepperkok, R, Lukas, C, Ellenberg, J, Bekker-Jensen, S, Mailand, N	Cell	2009