RAD-6: Pyrimidine synthesis and radiation sensitivity in Caenorhabditis elegans

In this study we describe the molecular identification of the rad-6 gene and reveal that it encodes the bifunctional UMP synthase protein, which carries catalytic activities for orotate phosphoribosyltransferase (OPRTase) and OMP decarboxylase (ODCase), key enzymes in the de novo pathway of pyrimidine synthesis. Mutations in genes encoding de novo pathway enzymes cause varying degrees of lethality and pleiotropic phenotypes in many organisms, including human. We have examined how the absence of rad-6 activity leads to both UV-C hypersensitivity and a decline in both metabolic rate and lifespan. We discuss how rad-6 mutants adapt to the loss of the de novo pathway through a dependency on pyrimidine salvage. We further establish that rad-6(mn160) mutants lack ODCase activity because they are resistant to the cytotoxic effects of 5-fluoroorotic acid (5-FOA). Our results have also led to the identification of a metabolic sensor affecting survival and metabolism, which is dependent on the maternal rad-6 genotype.

Source: BJ Gene - November 22, 2013 Category: Biochemistry Authors: A Merry, M Qiao, M Hasler, P E Kuwabara Tags: BJ Gene Source Type: research