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Nucleic Acids Research, 1993, Vol. 21, No. 17 4111-4118
© 1993

MOLECULAR BIOLOGY

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

Masashi Takao, Marija Abramic+, Malcolm Moos, Jr2, Vesna Rapic' Otrin, John C. Wootton1, Mary McLenigan, Arthur S. Levine and Miroslava Protic*

Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development Bethesda, MD 20892, USA 1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD 20892, USA 2Laboratory of Developmental Biology, Division of Cellular and Gene Therapy, Food and Drug Administration Bethesda, MD 20892, USA

* To whom correspondence should be addressed at: NIH, NICHD, Bldg. 6, Rm. 1A-15, Bethesda, MD 20892, USA

Received April 6, 1993. Revised June 30, 1993. Accepted June 30, 1993.

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.

+Present address: Department of Organic Chemistry and Biochemistry, Institute Rudjer BoSkovic', Zagreb, Croatia


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