Dataset Information


Guanine for DNA synthesis. A compulsory route through ribonucleotide reductase.

ABSTRACT: Two alternative pathways for the synthesis of dGTP and its incorporation into DNA were studied: guanine (Gua)----GMP----GDP----dGDP----dGTP----DNA and dG----dGMP----dGDP----dGTP----DNA. To determine the contribution of each pathway to DNA synthesis independently of each other, [14C]Gua and [3H]dG tracer experiments were performed in a double-mutant S-49 mouse T-lymphoma cell line, dGuo-L, with purine nucleoside phosphorylase (EC and dGTP-feedback-resistant ribonucleotide reductase (RR, EC In this cell line, dGTP pools can be selectively elevated by exogenous dG without affect RR and DNA synthesis. Although [3H]dG, but not [14C]Gua (up to 200 microM), readily expanded the cellular dGTP pool in a dose-dependent fashion in asynchronous cells, only a small fraction of the Gua flux into DNA was derived from [3H]dG, with the major fraction coming from [14C]Gua. H.p.l.c. analysis of G1- and partially enriched S-phase cells revealed that [3H]dGTP only accumulates in G1- but not in S-phase cells because of a rapid turnover of the dGTP pool during DNA synthesis. These results fail to provide evidence for cellular dGTP compartmentation and suggest that the pathway dG----dGMP----dGDP----dGTP alone has insufficient capacity to maintain DNA synthesis.

PROVIDER: S-EPMC1135346 | BioStudies | 1988-01-01

REPOSITORIES: biostudies

Similar Datasets

1986-01-01 | S-EPMC1146561 | BioStudies
| S-EPMC5852417 | BioStudies
1990-01-01 | S-EPMC1131500 | BioStudies
| S-EPMC6932243 | BioStudies
| S-EPMC3375575 | BioStudies
2013-01-01 | S-EPMC3630869 | BioStudies
| S-EPMC7866122 | BioStudies
2014-01-01 | S-EPMC3924892 | BioStudies
| S-EPMC6237811 | BioStudies
| S-EPMC8277322 | BioStudies