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M R Dyer

Publications and source records attributed to M R Dyer.

13 recordsLinked to original sources

Sequences of members of the human gene family for the c subunit of mitochondrial ATP synthase.

Subunit c is an intrinsic membrane component of ATP synthase, and in mammals it is encoded by two expressed nuclear genes, P1 and P2. Both genes encode the same mature c subunit, but the mitochondrial import pre-sequences in the precursors of subunit c are different. The DNA sequences of the human P1 and P2 genes are described. They occupy about 3.0 and 10.9 kb respectively of the human genome, and both genes are split into five exons. The human genome also contains about 14 related spliced pseudogenes, and the sequence of one such pseudogene related to P2 is described. Sequences flanking the 5' ends of the human P1 and P2 coding sequences each contain a CpG-rich island. Potential promoter elements (TATA and CCAAT boxes) are present in the 5' sequences of the P1 gene, but not that of P2, although there is no direct experimental evidence to show the involvement of these sequences in transcription of the genes.

Animals

DNA sequences of a bovine gene and of two related pseudogenes for the proteolipid subunit of mitochondrial ATP synthase.

The dicyclohexylcarbodi-imide-reactive proteolipid is a membrane subunit of mitochondrial ATP synthase. In cows it is encoded by two different nuclear genes known as P1 and P2. These genes are expressed in a tissue-specific fashion which reflects the embryonic origin of the tissues. The proteins that they encode are synthesized in the cytosol, and are precursors of the proteolipid that have different mitochondrial import sequences of 61 and 68 amino acids respectively. By use of gene-specific probes derived from the bovine P2 cDNA, regions containing corresponding parts of the bovine P2 gene have been isolated from a bovine genomic library, and their DNA sequences and those of flanking and intervening regions have been determined. The sequence contains four exons, which represent the cDNA sequence, spread over 3.8 kb of the bovine genome. Two of the introns are in the DNA sequence coding for the mitochondrial import sequence, and a third intron is in a sequence encoding an extramembranous structure between the two putative transmembrane alpha-helical domains of the mature proteolipid. An Alu-type repetitive element was detected at the extreme 5' end of the sequence. The bovine P1 and P2 genes for the dicyclohexylcarbodimide-reactive proteolipid of ATP synthase are members of a multiple gene family that also contains many pseudogenes. The bovine P1 gene has not been isolated, but two distinct P1 pseudogenes have been cloned and their DNA sequences have been determined. Both of them contain 'in-phase' stop codons and frame-shift mutations, and one of them bears the hallmarks of retroposition; it has no introns, it contains a poly(A) tract at its 3' end and it is flanked by direct DNA sequence repeats. The second P1 pseudogene is very unusual. It appears to be derived from a partially processed transcript and contains an intervening DNA sequence of 861 bp that corresponds in position with an intron in the human P1 gene. This pseudogene also could have been introduced by retroposition since its sequence is flanked by short direct repeats. However, it does not contain a poly(A) tract at its 3' end. An alternative, but less likely, explanation is that rather than being a retroposon, this sequence arose by duplication of an expressed gene at a time when it had only one intron.

ATP Synthetase Complexes

ATP synthase from bovine mitochondria: complementary DNA sequence of the mitochondrial import precursor of the gamma-subunit and the genomic sequence of the mature protein.

The gamma-subunit of mitochondrial ATP synthase is part of the extrinsic membrane sector of the enzyme F1-ATPase. It is a nuclear gene product. Complementary DNA clones encoding a precursor of the protein have been isolated from a bovine library. The initial partial clone was identified with a mixture of 32 synthetic oligonucleotides designed from the known protein sequence (Walker et al., 1985), and this isolate was then used to screen the library again in order to find a complete cDNA. The DNA sequence of a clone that encodes the entire mature protein has been established, and the deduced protein sequence agrees exactly with that determined by direct sequence analysis of protein isolated from bovine hearts (Walker et al., 1985). At the 3' ends of two independently isolated clones, alternative polyadenylation sites have been observed; otherwise, the DNA sequences of the clones are concordant. In common with many other mitochondrial proteins encoded in nuclear genes, the deduced protein sequence has an N-terminal extension that is absent from the mature protein. These presequences direct the protein to its appropriate mitochondrial compartment and are removed during the import process. The cDNA clone has been employed to isolate bovine genomic clones containing the gene for the gamma-subunit. From them, the DNA sequence has been established of a region encoding the mature protein and six amino acids in the presequence, but not the remainder of the proposed import sequence. This sequence extends over almost 10 kb and is divided into eight exons. Intron B between exons I and II contains a sequence that is related to long interspersed repetitive elements (LINEs) that have been described in other mammals. Human LINEs are usually flanked by directly repeated sequences with a poly(A) tract at their 3' ends, and these features are present in the bovine LINE which is truncated. This sequence contains an open reading frame encoding part of a protein that is closely related to a protein encoded in mouse LINEs, to reverse transcriptase, and to DNA binding proteins. We have also made a preliminary investigation by DNA hybridization of the number of sequences related to the bovine gene in both the bovine and human genomes. Under the experimental conditions employed, one fragment hybridized in digests of bovine DNA, and two to four bands were detected in digests of human DNA; these latter fragments have originated from either expressed genes or pseudogenes.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence

ATP synthase from bovine mitochondria: sequences of imported precursors of oligomycin sensitivity conferral protein, factor 6, and adenosinetriphosphatase inhibitor protein.

Oligomycin sensitivity conferral protein (OSCP), factor 6 (F6), and ATPase inhibitor protein are all components of the ATP synthase complex of bovine mitochondria. They are encoded in nuclear DNA. Complementary DNA clones encoding the precursors of these proteins have been isolated from a bovine library by using mixtures of synthetic oligonucleotides as hybridization probes, and their DNA sequences have been determined. The deduced protein sequences show that the OSCP, F6, and inhibitor proteins have N-terminal presequences of 23, 32, and 25 amino acids, respectively. These presequences are not present in the mature proteins. It is assumed that they serve to direct the proteins into the mitochondrial matrix. The cDNA clones have also been employed as hybridization probes to investigate the genetic complexity of the three proteins in cows and humans. These experiments indicate that the bovine and human inhibitor and bovine F6 proteins are encoded by single genes but suggest the possibility of the presence in both species of more than one gene (or pseudogenes) for the OSCP.

Adenosine Triphosphatases

The provision of crowns in the General Dental Service 1948-1988.

Crowns have been available under the NHS Regulations since the beginning of the NHS in 1948, and details of the incidence of the various types of crowns are held by the Dental Practice Board, Eastbourne. These records are analysed to show, among other trends, that the number of crowns increased to a peak in 1987, with the highest incidence in the 31-40 age group of patients. There was considerable variation in numbers of crowns provided by dentists in different areas of England and Wales, and the number of crowns provided varied with the age of the dentist. Relaxation in prior approval requirements before crowns could be provided does not seem to have had any marked long-term effect on the numbers of crowns provided.

Crowns