A model depicting the involvement of histone ubiquitylation in the cellular response to UV damage. (A). Upon UV irradiation, the histone ubiquitin ligase CUL4-DDB-ROC1 is recruited to the damaged chromatin through DDB2. Meanwhile, the ubiquitin moiety is cleaved from ubiquitylated H2A when cells sense the DNA damage. (B). CUL4-DDB-ROC1 ubiquitylates histones around the lesion, using ubiquitin released from H2A deubiquitylation. (C). Histone ubiquitylation by CUL4-DDB-ROC1 causes histone eviction from the damaged nucleosome. Meanwhile, Cul4 E3 ligase ubiquitylates DDB2 and XPC, resulting in the release of Cul4 E3 ligase from the damaged DNA and facilitating the binding of XPC to the damaged DNA. (D). After the repair processes, histone H2A around the DNA lesion is ubiquitylated in a Ring2 or Cul4 dependent manner.