Research ArticleDNA damage

RNF4-Dependent Hybrid SUMO-Ubiquitin Chains Are Signals for RAP80 and Thereby Mediate the Recruitment of BRCA1 to Sites of DNA Damage

Science Signaling  04 Dec 2012:
Vol. 5, Issue 253, pp. ra88
DOI: 10.1126/scisignal.2003485

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Hybrid Chains Mark the Spot

Posttranslational modifications play a key role in marking sites of DNA damage so that the DNA repair machinery can find the damaged area and effect repair. Guzzo et al. report a role for hybrid chains consisting of SUMO attached to a Lys63-linked diubiquitin as contributing to the recruitment of the protein RAP80, which in turn recruits the DNA repair protein BRCA1, to sites of damaged DNA. Knockdown of the E3 ligase RNF4, which synthesizes hybrid SUMO-ubiquitin linkages, prevented efficient recruitment of RAP80 and BRCA1 to sites of DNA damage induced by irradiation. This study defined a high-affinity interaction between a closely positioned pair of ubiquitin-interacting motifs and a SUMO-interacting motif in RAP80 that contributes to the recognition of sites of DNA damage.