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RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response.

ABSTRACT: The post-translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin-like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO-modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome-targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome-targeting is crucially required for the repair of TRF2-depleted dysfunctional telomeres by 53BP1-mediated non-homologous end joining.

SUBMITTER: Groocock LM

PROVIDER: S-EPMC4210088 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response.

Groocock Lynda M LM Nie Minghua M Prudden John J Moiani Davide D Wang Tao T Cheltsov Anton A Rambo Robert P RP Arvai Andrew S AS Hitomi Chiharu C Tainer John A JA Luger Karolin K Perry J Jefferson P JJ Lazzerini-Denchi Eros E Boddy Michael N MN

EMBO reports 20140408 5

The post-translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin-like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO-modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome-targeting motif within the RNF4 ...[more]

PMID: 24714598

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