A 127 KDA COMPONENT OF A UV-DAMAGED DNA-BINDING COMPLEX, WHICH IS DEFECTIVE IN SOME XERODERMA-PIGMENTOSUM GROUP-E PATIENTS, IS HOMOLOGOUS TO A SLIME-MOLD PROTEIN

A cDNA which encodes a approximately 127 kDa UV-damaged DNA-binding (U V-DDB) protein with high affinity for (6-4)pyrimidine dimers [Abramic' , M., Levine, A.S. & Protic', M., J. Biol. Chem. 266:22493-22500, 1991 ] has been isolated from a monkey cell cDNA library. The presence of t his protein in complexes bound to UV-damaged DNA was confirmed by immu noblotting. The human cognate of the UV-DDB gene was localized to chro mosome 11. UV-DDB mRNA was expressed in all human tissues examined, in cluding cells from two patients with xeroderma pigmentosum (group E) t hat are deficient in UV-DDB activity, which suggests that the binding defect in these cells may reside in a dysfunctional UV-DDB protein. Da tabase searches have revealed significant homology of the UV-DDB prote in sequence with partial sequences of yet uncharacterized proteins fro m Dictyostelium discoideum (44% identity over 529 amino acids) and Ory za sativa (54% identity over 74 residues). According to our results, t he UV-DDB polypeptide belongs to a highly conserved, structurally nove l family of proteins that may be involved in the early steps of the UV response, e.g., DNA damage recognition.