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HRad17, a Human Homologue of the Schizosaccharomyces pombe Checkpoint Gene rad17, Is Overexpressed in Colon Carcinoma¹

Dana-Farber Cancer Institute [S. B., M-S. C., D. A., Y. S., Y. W. W-K. W., J. Z., R. S., C. M-G., E. W., L. H., H. S., M. S. C., S-K. K., L. B. C.] and Beth Israel Deaconess Hospital [M. L.], Harvard Medical School, Boston, Massachusetts 02115, and Shionogi BioResearch Corporation, Lexington, Massachusetts 02421 [Y. L., X. Q., E. Y. S. C., K-M. L.]

Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.

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