Crystal structures of DDB1 bound to different substrate recognition subunits, including DDB2[18-20] and Cockayne Syndrome A (CSA)[18], reveal a common mode of binding in which the WD40 beta-propeller domain in DDB2 and CSA stabilizes association with DDB1 by mediating hydrophobic contacts with the BPA domain of DDB1 and by anchoring an amino-terminal helix-loop-helix motif that is inserted into a cavity at the interface between the BPA and BPC domains of DDB1. Here, DDB2 is linked to Cockayne syndrome type 1.