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.

DNA modified by the antitumor drug cisdiamminedichloroplatinum(II) (cis-DDP or cisplatin) was used to identify a factor in mammalian cells that binds to cis-DDP-damaged DNA and hence may play a role in repair. This factor selectively recognizes double-stranded DNA fragments modified by cis-DDP or [Pt(en)CI2J (en, ethylenediamine).Little or no binding occurs to unmodified double-stranded DNA or to DNA modified with the clinically ineffective compounds trans-DDP and [Pt(dien)Cl]Cl (dien, diethylenetriamine). Low levels of binding to single-stranded DNA modified by cis-DDP are observed. The apparent molecular mass of the factor in a variety of mammalian cells is -100 kDa, as determined by modified Western blotting. Two recombinant phage have been isolated from a human B-cell Agtll library by using a cis-DDP-modified DNA restriction fragment as a probe. The two clones have insert sizes of 1.88 and 1.44 kilobases and are aligned at their 5' ends. The polypeptides encoded by the recombinant phage exhibit DNA binding properties similar to those of the cellular factor identified in crude extracts prepared from mammalian cells. Northern analysis with one ofthe clones revealed an mRNA of 2.8 kilobases that is conserved in humans and rodents. The methods used here should be applicable in studies of other damage-specific DNA binding proteins.cis-Diamminedichloroplatinum(II) (cis-DDP or cisplatin) is a clinically important antitumor drug used for the treatment of several human cancers, especially those of genitourinary origin (1). The biological target for cis-DDP is generally accepted to be DNA (2), and considerable information is now available on binding of the drug to DNA and the structures of its major adducts (3). Despite this progress, much remains to be learned about the specificity of cis-DDP for certain tumors as well as its activity relative to other platinum compounds.Both cis-DDP and its biologically inactive trans isomer bind to DNA in vitro and in vivo, and the resultant adducts can serve as termination sites for DNA polymerase (4). DNA replication is inhibited to similar extents by both cis and trans-DDP in vivo at the same bound drug/nucleotide ratio process or repair the DNA adducts of these various platinum complexes.To address this issue, we set out to identify cellular factors that could play a role in processing DNA modified by platinum(II) complexes. Previously identified prokaryotic repair systems such as the UvrABC excision nuclease are known to excise adducts from DNA modified by cis-but not trans-DDP (6). In addition, one component of the repair complex, UvrA, possesses specific binding properties for DNA modified by damaging agents such as ultraviolet radiation (7,8). It therefore seemed reasonable that, in mammalian cells, a similar damaged DNA binding factor would exist having sufficient generality to recognize cis-DDP modified DNA as an initial step leading to repair.Our approach has involved the use of DNA modified by cis-DDP as a probe for DNA binding factors present in crude mammalian...

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An X-ray crystallographic study of the first examples of complexes containing co-ordinated nitrobenzene, [Zn(PhN02)2(0TeF5)2]2 and Zn(PhN02)3(0TeF5)2, has proven that nitrobenzene can function as a bidentate (0,O') ligand as well as a monodentate (0) ligand.

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. Can. J. Chem. 67, 2023 (1989). An orthorhombic crystalline modification of [(PS)H+ IIOTeFS-] was studied by single crystal X-ray diffraction ((PS)H+ = protonated 1,8-bis(dimethylamino)naphthalene): orthorhombic, space group Cmcm, a = 8.607(2), b = 14.048(3), c = 13.365(2) A, Z = 4, T = -130°C. The structural parameters for the anion and cation in this modification (Mod-B) are very similar to those for the previously reported triclinic modification of this salt (Mod-A). However, variable temperature IR spectra for Mod-B suggest that the OTeFS-anion is exhibiting a two-site O/Fa, interchange above -70°C. Solid-state ' 9~ NMR spectra suggest that this interchange may be as rapid as lo4-lo5 s-I at room temperature. [Traduit par la revue]

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