Mixed ubiquitin chains regulate DNA repair

Abstract

Diverse linkage in polyubiquitin chain structure gives cells an unparalleled complexity to virtually modulate all aspects of cell biology. Substrates can be covalently modified by ubiquitin chains of different topology. Proper DNA damage response takes advantage of this regulatory system and heavily relies on ubiquitin-based signaling. Moreover, increasing evidence suggests that chain specificity dictates DNA repair outcome. In this issue of Genes & Development, Wu and colleagues (pp. 1702-1717) show that Cezanne and Cezanne2, two paralogous deubiquitinating enzymes that are recruited to sites ofDNAdamage, ensure proper local polyubiquitin chain composition for downstreamDNArepair protein assembly. Their study offers a key insight into the mechanismof crosstalk between linkage-specific ubiquitylation atDNAdamage sites,while simultaneously raising important questions for future research.