Ixr1, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin.
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.
Brown
S J
SJ
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
Kellett
P J
PJ
Lippard
S J
SJ
D000595:Amino Acid Sequence; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology*; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D004271:DNA, Fungal / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D018736:DNA Adducts; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006609:High Mobility Group Proteins; C082364:IXR1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C057270:cisplatin-DNA adduct; D004247:DNA; D002945:Cisplatin