The role of Cockayne syndrome group A (CSA) protein in transcription-coupled nucleotide excision repair

•CSA is a specific factor for transcription-coupled nucleotide excision repair.•CSA has seven WD40 repeat motifs and beta-propeller architecture.•The CSA-DDB1-Cul4A-Roc1 complex exhibits ubiquitin ligase activity.•CSA is required for the recruitment of UVSSA-USP7 to stalled RNA polymerase II.

Nucleotide excision repair (NER) removes a variety of DNA lesions, including ultraviolet-induced cyclobutane pyrimidine dimers. NER comprises two subpathways: transcription-coupled NER (TC-NER) and global genome NER. TC-NER efficiently removes lesions from the transcribed strands of active genes. Mutations in Cockayne syndrome groups A and B genes (CSA and CSB) result in defective TC-NER. In mammalian cells, TC-NER is presumably initiated by the arrest of RNA polymerase II at a lesion on the transcribed strand of an active gene, but the molecular mechanism underlying TC-NER remains unclear. The CSA protein has seven WD40 repeat motifs and beta-propeller architecture. A protein complex consisting of CSA, DDB1, cullin 4A, and Roc1 exhibits ubiquitin ligase activity. The role of CSA protein in TC-NER is described in this review.