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B Malfoy

Publications and source records attributed to B Malfoy.

78 records · Page 5Linked to original sources
PubMed1981

Immunochemical studies of DNA modified by cis-dichlorodiammineplatinum(II) in vivo and in vitro.

Two rabbits were immunized with native DNA modified in vitro by cis-dichlorodiammineplatinum(II) (cis-Pt). The interactions between the antiserum and several natural and synthetic nucleic acids were studied primarily by radioimmunoassays. Native DNA's modified by platinum compounds with labile groups in the cis position are recognized by the antiserum. No cross-reaction is found with native DNA's substituted by other platinum compounds [trans-dichlorodiammineplatinum(II), cis-diamminotetrachloroplatinum(IV), and chlorodiethylenetriamminoplatinum(II)] and with natural and synthetic modified polyribonucleotides. cis-Pt-modified oligodeoxyribonucleotides and enzymatically hydrolyzed cis-Pt-modified native DNA do not bind to the antiserum. cis-Pt-modified double-stranded synthetic polydeoxyribonucleotides are either hardly recognized or not recognized at all. The antiserum recognized a modified double-stranded helix in DNA which is not formed in several modified synthetic DNA's and RNA's. At least two different antigenic determinants are present in cis-Pt-modified DNA at a ratio of cis-Pt to bases equal to 0.05. Finally, the antiserum does not react with in vivo cis-Pt-modified DNA.

Animals↗
PubMedDate not supplied

Z-DNA immunoreactivity in rat tissues.

Recently, it has been shown that natural and synthetic deoxynucleotide polymers can adopt a left-handed helical structure (termed Z-DNA) in appropriate conditions (see, for example, refs 1 and 2 and the references therein). In contrast to the more familiar right-handed B-DNA, Z-DNA is strongly immunogenic, and polyclonal and monoclonal antibodies against Z-DNA have been elicited. By using such antibodies, immunoreactivity for Z-DNA has been detected in the polytene chromosomes of two dipteran species, in the macronucleus of a ciliated protozoon, and in certain plant nuclei (cited in ref. 11). In view of the possible importance of Z-DNA as a genomic regulatory signal, it would be highly desirable to know whether Z-DNA also occurs in mammals. We have therefore initiated an immunohistochemical study of various rat tissues by using three antisera specific for Z-DNA, and the peroxidase-antiperoxidase technique for visualization of tissue-bound antibodies. Here we demonstrate that the nuclei of many, but not all, types of rat cells exhibit Z-DNA immunoreactivity, suggesting that Z-DNA may exist naturally in mammalian chromatin.

Animals↗
PubMedDate not supplied

Ring-opened alkylated guanine is not repaired in Z-DNA.

Since the discovery of Z-DNA by X-ray analysis of the alternated hexanucleotide d(C-G)3 crystals, numerous studies have shown that fragments of natural DNAs can adopt the Z conformation, topological constraints being a major factor stabilizing this conformation. Immunochemical assays using antibodies to Z-DNA provide strong evidence for the presence of Z fragments in chromosomes. The biological role of Z-DNA is not yet known, but it might be involved in gene regulation. Proteins which bind specifically to Z-DNA have been isolated and interactions between Z-DNA and several cellular proteins have been studied. The ability of DNA repair enzymes to maintain the genome's integrity is of major importance to the cell. On alkylation of DNA by chemical carcinogens such as dimethyl sulphate, methyl methanesulphonate, methylnitrosourea or methylnitrosoguanidine, the main target is the N7 of the guanosine residue, yielding 7-methylguanine (mG). In alkaline conditions, the imidazole ring of mG opens up, yielding the ring-opened form 2,6-diamino-4-oxo-5-methylformamidopyrimidine (rom7G); this lesion is a block to DNA replication. It occurs in vivo and is enzymatically removed by the DNA glycosylase. Here we report that the lesion is not excised when present in DNA in the left-handed Z conformation.

DNA Repair↗