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

• Published in: Mechanisms of ageing and development Vol. 134; no. 5-6; pp. 196 - 201
• Main Author: Saijo, Masafumi
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.05.2013
• Subjects: Amino Acid Motifs; Animals; Cockayne Syndrome - genetics; Cockayne Syndrome - metabolism; Cockayne Syndrome - pathology; Cullin Proteins - genetics; Cullin Proteins - metabolism; DNA Helicases - genetics; DNA Helicases - metabolism; DNA Repair - physiology; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Humans; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Nucleotide excision repair; Poly-ADP-Ribose Binding Proteins; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - physiology; Transcription-coupled repair; Ubiquitin ligase; UV-sensitive syndrome; WD40 repeat; Cul4A; TC-NER; Pol II; Ubiquitin ligase; HLH; UVSS; CRL4; GG-NER; Nucleotide excision repair; UV-DDB; Transcription-coupled repair; CS; UV-sensitive syndrome; XP; NER; DCAF; CSN; WD40 repeat
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2013.03.008

•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.