Disease relevance of NUC1

• The deduced polypeptide, NucA, had a molecular weight of 29,650, presented a presumptive signal peptide in its N-terminal region and showed homology to the products of the nuc gene from Serratia marcescens and the NUC1 gene from Saccharomyces cerevisiae [1].

High impact information on NUC1

• Deletion of NUC1 diminishes apoptotic death when mitochondrial respiration is increased but enhances necrotic death when oxidative phosphorylation is repressed, pointing to dual--lethal and vital--roles for EndoG [2].
• Here, we show that the yeast homolog of EndoG (Nuc1p) can efficiently trigger apoptotic cell death when excluded from mitochondria [2].
• Nuc1p induces apoptosis in yeast independently of metacaspase or of apoptosis inducing factor [2].
• The overproduced PIF1 protein, which is firmly associated with insoluble mitochondrial structures, has been partially purified in a mitochondrial nuclease deficient nuc1 strain by a procedure including solubilization by urea and renaturation by dialysis at alkaline pH [3].
• The amino acid sequence shows homology with two yeast proteins whose functions are analogous to that of the NUC-1 protein [4].

Biological context of NUC1

• NUC1 is very poorly expressed, consistent with the codon usage bias determined from the DNA sequence and our previous determination of the number of enzyme molecules per cell [5].
• The inferred amino acid sequence of NUC1 predicts that the nuclease is basic, rich in prolines, of average hydrophobicity, and has a molecular weight for the primary translation product of 37,209 daltons [5].
• The NUC1 locus is located in the distal portion of the left arm of Chromosome X and encodes the major nuclease found in mitochondria [5].
• Mapping of the 5' terminus of the NUC1 mRNA reveals that the mRNA has a long 400 base untranslated leader in which are found three open reading frames, each initiated by an AUG. The possibility that these upstream open reading frames contribute to the poor expression of the NUC1 gene is discussed [5].
• In particular, the gradient of gene conversion at omega was most affected by the absence of the NUC1 nuclease [6].

Anatomical context of NUC1

• Here we present the finding that nuclear recessive mutations in the NUC1 gene, which encodes the major nonspecific nuclease of yeast mitochondria, resulted in at least a 10-fold increase in amounts of the L-A dsRNA and its encoded coat protein [7].
• The increase in L-A expression in nuc1 strains was similar to that observed in strains with mutations in the nuclear gene encoding the most abundant outer mitochondrial membrane protein, porin. nuc1 mutations did not affect the level of porin in the mitochondrial outer membrane [7].

Associations of NUC1 with chemical compounds

• Both NUC1 and nuc1 strains containing the L-A genome exhibited an increase in coat protein abundance and a concomitant increase in L-A dsRNA when the cells were grown on a nonfermentable carbon source rather than on glucose, an effect independent of the increase in coat protein due to nuc1 mutations or to the absence of M [7].

Other interactions of NUC1

• The DNA-binding activity of NUC-1 has not been directly demonstrated; however, results of deletion analysis, sequence analysis of the nuc-1 mutant alleles, and strong sequence similarity with the Saccharomyces cerevisiae PHO4 protein strongly suggest that the basic helix-loop-helix motif of NUC-1 forms a DNA-binding domain [8].

References