IDENTIFICATION OF SEVERAL HUMAN HOMOLOGS OF HAMSTER DNA DAMAGE-INDUCIBLE TRANSCRIPTS - CLONING AND CHARACTERIZATION OF A NOVEL UV-INDUCIBLECDNA THAT CODES FOR A PUTATIVE RNA-BINDING PROTEIN

Low Patio hybridization subtraction technique was previously used in t his laboratory to enrich and isolate a number of low abundance UV-indu cible hamster transcripts (Fornace, A. J., Jr., Alamo, I. J., and Holl ander, M. C. (1988) Proc. Natl. Acad, Sci. U. S. A. 85, 8800-8804) tha t led to the identification and cloning of five important hamster and human GADD genes (Fornace, A. J., Jr., Nebert, D. W., Hollander, M. C, , Luethy, J. D., Papathanasiou, M., Fargnoli, J., and Holbrook, N. J. (1989) Mol, Cell. Biol. 9, 4196-4205), In this study we have character ized the remaining DNA damage-inducible (DDI) transcripts. Of the 24 D DI clones, 3 clones (A13, A20, and A113) representing different region s of the same hamster cDNA exhibited near perfect homology to human p2 1(WAF1/CIP1) cDNA. The DDI clones A26, A88, and A99 displayed very hig h sequence homologies with the human proliferating nuclear antigen, ra t translation initiation factor-5 (eIF-5), and human thrombomodulin, r espectively, whereas clones A29 and A121 matched with express sequence tagged sequences of unknown identity, The DDI clones A18, 106, and A1 07 were different isolates of the same hamster cDNA (hereafter referre d to as A18) and displayed high sequence homology with the members in the heterogeneous ribonucleoprotein (hnRNP) family, Using the hamster A18 partial-length cDNA as a probe, we screened human fibroblast cDNA library and isolated the corresponding full-length human cDNA. The ded uced amino acid sequence revealed that the putative protein contains a ll the canonical features of a novel glycine-rich hnRNP. The A18 mRNA levels mere specifically increased in response to DNA damage induced b y UV irradiation or UV mimetic agents, Thus the putative A18 hnRNP is the first hnRNP whose mRNA is specifically regulated in response to UV -induced DNA damage; accordingly, it may play some role in repair of W -type DNA damage.