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J C Fiddes

Publications and source records attributed to J C Fiddes.

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Nucleotide sequence of bacteriophage G4 DNA.

The 5,577 nucleotide long sequence of bacteriophage G4 DNA has been determined using the 'plus and minus' and chain termination methods of DNA sequencing. This sequence has been compared with that of the closely related bacteriophage phiX174 (refs 1, 55). In the coding regions there is an average of 33.1% nucleotide sequence differences between the two genomes, but the distribution of these changes is not random and the sequence of some genes is more conserved than others. There is less sequence similarity between the untranslated intergenic regions of G4 and phiX174, but despite this the sequences of the J/F, F/G and H/A untranslated spaces in both genomes have similar sized hairpin loops, which may be related to their function.

Bacteriophages↗

Nucleotide sequence of the J gene and surrounding untranslated regions of phage G4 DNA: comparison with phage phiX174.

A 290 nucleotide long region of the bacteriophage G4 genome including the end of the overlapping genes D and E, the entire gene J and the untranslated region between genes J and F has been sequenced and compared with the same region in bacteriophage phiX174. Deletions, insertions, duplications and single base changes in G4 relative to phiX174 have resulted in the following changes: the loss of the phiX174 overlapping gene Dtermination and gene J initiation codons, resulting in their separation by 32 untranslated nucleotides; the deletion of one third of the gene J coding region, so that the G4 protein is only 24 amino acids long compared with 37 amino acids in phiX174; and the establishment of a long untranslated region between G4 genes J and F, which despite many nucleotide changes retains the ability to form a stable hairpin loop in the same place and with the same geometry as in phiX174. The G4 overlapping gene E is longer than in phiX174 and extends beyond gene D. Sixteen nucleotides at the end of genes D and E in phiX174 are duplicated in G4 before gene J.

Base Sequence↗

Nucleotide sequences of the separate origins of synthesis of bacteriophage G4 viral and complementary DNA strands.

Bacteriophage G4 has physically separated origins of synthesis of its viral and complementary DNA strands. Chain termination and "plus and minus" DNA sequencing methods have been used to obtain the nucleotide sequence of these two origins. The unique origin at which the complementary DNA strand is initiated has located in the untranslated region between genes F and G. This sequence, which has considerable secondary structure, contains a stretch which is complementary to the RNA primer that is observed during synthesis in vitro of the G4 complementary DNA strand [Bouché, J.P., Rowen, L. & Kornberg, A. (1978) J. Biol. Chem., in press]. This G4 origin shows extensive sequence homology with the bacteriophage lambda origin of DNA replication [Denniston-Thompson, K., Moore, D. D., Kruger, D. E., Furth, M. E. & Blattner, F. R. (1977) Science 198, 1051-1056]. The sequence around the site in gene A at which G4 viral DNA strand synthesis is initiated by the nicking action of the cistron A protein is very similar to that of bacteriophage phiX174. An (A + T)-rich stretch flanked by (G + C)-rich sequences may be involved in the interaction between the DNA and protein.

Bacteriophages↗

Evolution of the genes for the beta subunits of human chorionic gonadotropin and luteinizing hormone.

Nucleotide sequence comparisons of the single gene for the human luteinizing hormone gene beta subunit with two of the seven genes for the human chorionic gonadotropin beta subunit suggest that the beta human chorionic gonadotropin genes have evolved from an ancestral beta luteinizing hormone gene by a series of selected changes with very little neutral drift. Moreover, the 24 amino acid carboxy-terminal extension of the human chorionic gonadotropin beta subunit appears to have arisen by a single base deletion that incorporated the 3'-untranslated region of the ancestral beta luteinizing hormone gene into the coding region.

Base Sequence↗

Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor.

The mammalian atrium is an endocrine organ that may be involved in the control of blood pressure and extracellular fluid volume. A series of peptides, which seem to be associated with atrium-specific secretory granules, have potent natriuretic, diuretic and smooth muscle relaxant activities. Sequence determination of several of these peptides, which range from 21 to 126 amino acids long, shows that they form a family, derived from a common precursor. Rat and human complementary DNAs that encode the precursor to the various peptides, collectively called atrial natriuretic factors (ANFs), have been cloned. Nucleotide sequencing showed that the ANFs are located at the C-terminus of a polypeptide of relative molecular mass 13,000. We describe here the isolation and characterization of the corresponding human gene. Two introns interrupt the gene; one is located in the region coding for the N-terminus of the precursor and the other separates the codon for the C-terminal tyrosine from the rest of the peptide.

Amino Acid Sequence↗

Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth.

Angiogenesis, the formation of new capillaries, which is observed in embryonic and injured tissue and is particularly prominent in the vicinity of solid tumours, involves the migration and proliferation of capillary endothelial cells. It is probably triggered by agents, such as basic fibroblast growth factor (bFGF), thought to be released from tissues adjacent to proliferating capillaries. As well as being a potent inducer of cell division in capillary endothelial cells in vitro, bFGF can act as an angiogenic agent in vivo. It is present in a wide variety of richly vascularized tissues including brain, pituitary, retina, adrenal gland, kidney, corpus luteum, placenta and various tumours. So far, however, the normal bFGF-producing cell species in these tissues have not been identified. We report here that capillary endothelial cells express the bFGF gene, that they produce and release bFGF and that bFGF derived from them can stimulate the proliferation of capillary endothelial cells. We conclude that bFGF can act as a self-stimulating growth factor for capillary endothelial cells, and that it is possible that the formation of new capillaries is induced by capillary endothelial cells themselves.

Animals↗