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Science 30 July 1993:
Vol. 261. no. 5121, pp. 603 - 605
DOI: 10.1126/science.8342024
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Articles

Science, Vol 261, Issue 5121, 603-605
Copyright © 1993 by American Association for the Advancement of Science

articles

Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin

SJ Brown, PJ Kellett, and SJ Lippard

Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.

Structure-specific recognition proteins (SSRPs) bind to DNA containing intrastrand cross-links formed by the anticancer drug cisplatin. A yeast gene encoding an SSRP, designated IXR1, was cloned and sequenced. The Ixr1 protein, a member of the high mobility group-box protein family, bound specifically to DNA modified with cisplatin but not inactive platinum compounds. A yeast strain with an inactivated IXR1 gene was half as sensitive to cisplatin and accumulated one-third as many platinum-DNA lesions after treatment with cisplatin as the parental strain. These findings suggest that SSRPs play a role in mediating the cytotoxicity of cisplatin.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)