Cockayne syndrome (CS) is a recessive disorder that results in deficiencies in transcription-coupled nucleotide excision repair (TC-NER), a subpathway of nucleotide excision repair, and cells from CS patients exhibit hypersensitivity to UV light. CS group B protein (CSB), which is the gene product of one of the genes responsible for CS, belongs to the SWI2/SNF2 DNA-dependent ATPase family and has an ATPase domain and an ubiquitinbinding domain (UBD) in the central region and the C-terminal region, respectively. The C-terminal region containing the UBD is essential for the functions of CSB. In this study, we generated several CSB deletion mutants and analyzed the functions of the C-terminal region of CSB in TC-NER. Not only the UBD but also the C-terminal 30-amino acid residues were required for UV light resistance and TC-NER. This region was needed for the interaction of CSB with RNA polymerase II, the translocation of CS group A protein to the nuclear matrix, and the association of CSB with chromatin after UV irradiation. CSB was modified by small ubiquitin-like modifier 2/3 in a UV light-dependent manner. This modification was abolished in a CSB mutant lacking the C-terminal 30 amino acid residues. However, the substitution of lysine residues in this region with arginine did not affect SUMOylation or TC-NER. By contrast, substitution of a lysine residue in the N-terminal region with arginine decreased SUMOylation and resulted in cells with defects in TC-NER. These results indicate that both the most C-terminal region and SUMOylation are important for the functions of CSB in TC-NER.

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Dishevelled (Dvl) is a positive regulator of the canonical Wnt pathway that downregulates the phosphorylation of β‐catenin and its subsequent degradation. Dvl contains an N‐terminal DIX domain, which is involved in its homooligomerization and interactions with regulators of the Wnt pathway. The crystal structure of a Y27W mutant of the Dishevelled2 DIX domain (DIX‐Y27W) has been determined at 1.64 Å resolution. DIX‐Y27W has a compact ubiquitin‐like fold and self‐associates with neighbouring molecules through β‐bridges, resulting in a head‐to‐tail helical molecular arrangement similar to previously reported structures of DIX domains. Glu23 of DIX‐Y27W forms a hydrogen bond to the side chain of Trp27, corresponding to the Glu762…Trp766 hydrogen bond of the rat Axin DIX domain, whereas Glu23 in the Y27D mutant of the Dishevelled2 DIX domain forms a salt bridge to Lys68 of the adjacent molecule. The high‐resolution DIX‐Y27W structure provides details of the head‐to‐tail interaction, including solvent molecules, and also the plausibly wild‐type‐like structure of the self‐association surface compared with previously published Dvl DIX‐domain mutants.

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