ISSN:
1573-4927
Keywords:
cytidine 5′-triphosphate synthetase
;
Chinese hamster cells
;
pyrimidine metabolism
;
K m mutants
;
nucleotide pools
;
feedback inhibition
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract Following chemical mutagenesis and multiple-step indirect selection, four clones of Chinese hamster V79 cells were isolated which exhibited auxotrophy for thymidine, deoxycytidine, or deoxyuridine but not for cytidine or uridine. All were resistant to uridine, 3-deazauridine, 5-fluorouridine, thymidine, and cytosine arabinoside at concentrations that were toxic to wild-type V79 cells. The cytidine 5′-triphosphate (CTP) and deoxycytidine 5′-triphosphate (dCTP) pools in the mutants were expanded, but the uridine 5′-triphosphate (UTP) pool either decreased or remained unchanged relative to the wild-type level. Furthermore, since the parental cells appear to be deficient in dCMP deaminase activity and CTP (or one of its metabolites) has been shown to inhibit uridine 5′-diphosphate (UDP) reduction, an elevated CTP level should lead to the observed thymidine auxotrophy. It also explains the joint resistance of mutant clones to thymidine and cytosine arabinoside. The change in the ratio of intracellular dCTP to thymidine 5′-triphosphate (dTTP) may be responsible for the elevation in the rates of spontaneous mutations in these mutants.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00485854
