A cDNA which encodes á 127 kDa UV-damaged DNA-binding (UV-DDB) protein with high affinity for (6-4)pyrlmidine 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 this protein in complexes bound to UV-damaged DNA was confirmed by immunobiotting. The human cognate of the UV-DDB gene was localized to chromosome 11. UV-DDB mRNA was expressed in all human tissues examined, including cells from two patients with xeroderma pigmentosum (group E) that are deficient in UV-DDB activity, which suggests that the binding defect in these cells may reside in a dysfunctional UV-DDB protein. Database searches have revealed significant homology of the UV-DDB protein sequence with partial sequences of yet uncharacterized proteins from Dictyostellum discoldeum (44% Identity over 529 amino acids) and Oryza satlva (54% identity over 74 residues). According to our results, the UV-DDB polypeptide belongs to a highly conserved, structurally novel family of proteins that may be involved in the early steps of the UV response, e.g., DNA damage recognition.
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