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Biomedical subjects

N Zhu

Publications and source records attributed to N Zhu.

78 records · Page 5Linked to original sources
PubMed1992

Recombination of 4p16 DNA markers in an unusual family with Huntington disease.

The Huntington disease (HD) mutation has been localized to human chromosome 4p16, in a 6-Mb region between the D4S10 locus and the 4p telomere. In a report by Robbins et al., a family was identified in which an affected individual failed to inherit three alleles within the 6-Mb region originating from the parental HD chromosome. To explain these results, it was suggested that the HD locus (HD) lies close to the telomere and that a recombination event took place between HD and the most telomeric marker examined, D4S90. As a test of this telomere hypothesis, we examined six members of this family, five of whom are affected with HD, for the segregation of 12 polymorphic markers from 4p16, including D4S169, which lies within 80 kb of the 4p telomere. We separated, in somatic cell hybrids, the chromosomes 4 from each family member, to determine the phase of marker alleles on each chromosome. We excluded nonpaternity by performing DNA fingerprint analyses on all six family members, and we found no evidence for chromosomal rearrangements when we used high-resolution karyotype analysis. We found that two affected siblings, including one of the patients originally described by Robbins et al., inherited alleles from the non-HD chromosome 4 of their affected parents, throughout the 6-Mb region. We found that a third affected sibling, also studied by Robbins et al., inherited alleles from the HD chromosome 4 of the affected parent, throughout the 6-Mb region. Finally, we found that a fourth sibling, who is likely affected with HD, has both a recombination event within the 6-Mb region and an additional recombination event in a more centromeric region of the short arm of chromosome 4. Our results argue against a telomeric location for HD and suggest that the HD mutation in this family is either associated with DNA predisposed to double recombination and/or gene conversion within the 6-Mb region or is in a gene that is outside this region and that is different from that mutated in most other families with HD.

Adult↗
PubMed1991

The nadI region of Salmonella typhimurium encodes a bifunctional regulatory protein.

Mutants of the nadI and pnuA genes were independently isolated on the basis of defects in repression of NAD biosynthetic genes and defects in transport nicotinamide mononucleotide (NMN). The mutations map at min 99 on the Salmonella chromosome, and the affected regions appear to be cotranscribed. Some pairs of nadI and pnuA mutations complement, suggesting the existence of independent functions. However, cis/trans tests with particular mutations provide evidence that both repressor and transport functions are actually performed by a single bifunctional protein. (This result confirms sequencing data of Foster and coworkers [J. W. Foster, Y. K. Park, T. Fenger, and M. P. Spector, J. Bacteriol. 172:4187-4196, 1990]). We have designated the gene for this bifunctional protein nadI and distinguish the regulatory and transport defects with phenotypic designations (R and T). When a nadI(R- T+) mutation (eliminating only repression function) is placed cis to a superrepressor mutation, nadI(Rs T-), the superrepression phenotype is lost. In contrast, placement of R- and Rs T- mutations in trans allows full superrepression. This result suggests that the transport function (eliminated by the Rs T- mutation) and the repression function are provided by the same protein. Insertion mutations in the promoter-proximal repressor region of the nadI gene eliminate transport function unless the inserted element can provide both for both transcription and translation start signals; this finding suggests that there is no transcriptional or translational start between the regions encoding repression and transport functions.

Bacterial Proteins↗
PubMed1991

Activity of the nicotinamide mononucleotide transport system is regulated in Salmonella typhimurium.

Transport of nicotinamide mononucleotide (NMN) requires two functions, NadI(T) and PnuC. The PnuC protein is membrane associated, as judged by isolation of active TnphoA gene fusions and demonstration that the fusion protein is membrane associated. The PnuC function appears to be the major component of the transport system, since mutant alleles of the pnuC gene permit NMN transport in the absence of NadI(T) function. We present evidence that the activity of the NMN transport system varies in response to internal pyridine levels (presumably NAD). This control mechanism requires NadI(T) function, which is provided by a bifunctional protein encoded by the nadI gene (called nadR by Foster and co-workers [J. W. Foster, Y. K. Park, T. Fenger, and M. P. Spector, J. Bacteriol. 172:4187-4196]). The nadI protein regulates transcription of the nadA and nadB biosynthetic genes and modulates activity of the NMN permease; both regulatory activities respond to the internal pyridine nucleotide level.

Bacterial Proteins↗
PubMed1989

Genetic characterization of the pnuC gene, which encodes a component of the nicotinamide mononucleotide transport system in Salmonella typhimurium.

The pnuC gene, which encodes a component of the nicotinamide mononucleotide transport system, has been mapped and oriented. The gene order of the pnuC region, which is at min 17 of the Salmonella chromosome, is nadA-pnuC-aroG-gal. Polarity tests, with pnuC::Mu d-lac operon fusions, reveal that the pnuC gene is the promoter distal gene in an operon with the nadA gene, which encodes the second enzyme of the pyridine biosynthetic pathway. The nadA pnuC operon is regulated by the NadI repressor. The pnuC gene also has its own promoter, since strains with a nadA::Tn10d(Tc) insertion still express the pnuC gene at a low, unregulated level.

Bacterial Proteins↗
PubMed1988

Identification of a repressor gene involved in the regulation of NAD de novo biosynthesis in Salmonella typhimurium.

Mutations at the nadI locus affect expression of the first two genes of NAD synthesis, nadA and nadB, which are unlinked. Genetic data imply that the regulatory effects of nadI mutations are not due to indirect consequences of physiological alterations. Two types of mutations map in the nadI region. Common null mutations (nadI) show constitutive high-level expression of the nadB and nadA genes. Rare nadIs mutations cause constitutive low-level expression of nadB and nadA. Some nadIs mutations shut off the expression of the biosynthetic genes sufficiently to cause a nicotinic acid auxotrophy. Spontaneous revertants of auxotrophic nadIs mutants have a NadI- phenotype, including some with deletions of the nadI locus. The nadI locus encodes a repressor protein acting on the unlinked nadA and nadB genes.

Cloning, Molecular↗