High impact information on tam

• The tam mutation reduces the transcription of a repressor gene, extramacrochaetae, and causes enlargement of a proneural cluster where supernumerary precursor cells emerge, resulting in extra mechanosensory organs in the fly [1].
• In this study, we report the isolation and analysis of the tamou (tam) gene that encodes a cell-cell junction-associated protein, which is homologous to mammalian ZO-1, a member of the membrane-associated guanylate kinase homolog family [1].
• Both subunits have been cloned and characterized in a variety of model systems, and genetic mutants of the catalytic subunit were first identified in Drosophila, as chemically induced mutations that disrupt larval behavior (tamas) [2].
• DNA polymerase gamma, Pol gamma, is the key replicative enzyme in animal mitochondria [2].
• The DNA polymerase is inhibited by 200 mM NaCl and is unable to use poly(rA)/oligo(dT) as a template, thus differentiating it from DNA polymerase gamma [3].

Biological context of tam

• The mutation responsible for these phenotypes was mapped to the lethal complementation group l(2)34Dc, which we renamed tamas (translated from Sanskrit as "dark inertia") [4].
• Overexpression of the catalytic subunit of DNA polymerase gamma results in depletion of mitochondrial DNA in Drosophila melanogaster [5].
• Concurrent achievement of maximal activity and processivity by mitochondrial DNA polymerase in the presence of binding protein suggests that DNA polymerase gamma, like other replicative DNA polymerases, associates with accessory factors in vivo to catalyze efficient and processive DNA synthesis [6].

Anatomical context of tam

• The polypeptide is properly targeted to mitochondria, yet the large excess of pol gamma-alpha does not interfere with mtDNA replication under these conditions where the endogenous polypeptide is apparently present in amounts that exceed of the demand for its function in the cell [5].

Other interactions of tam

• The nuclear-encoded DNA polymerase gamma (DNA POL gamma) is the sole DNA polymerase required for the replication of the mitochondrial DNA [7].
• Our results indicate that the stimulation of Drosophila DNA polymerase gamma by single-stranded DNA-binding protein results primarily from an increased rate of primer recognition and binding [6].

Analytical, diagnostic and therapeutic context of tam

• In striking contrast, overexpression of pol gamma-alpha at the same level in transgenic flies interferes with the mtDNA replication process, presumably by altering the mechanism of DNA synthesis, suggesting differential requirements for, and/or regulation of, mtDNA replication in Drosophila cell culture versus the developing organism [5].

References