Woods R A, Roberts D G, Friedman T, Jolly D, Filpula D
Mol Gen Genet. 1983;191(3):407-12. doi: 10.1007/BF00425755.
Yeast mutants lacking activity of the enzyme hypoxanthine:guanine phosphoribosyltransferase (H:G-PRT) have been isolated by selecting for resistance to 8-azaguanine in a strain carrying the wild type allele, ade4%, of the gene coding for amidophosphoribosyltransferase (PRPPAT), the first enzyme of de novo purine synthesis. The mutants excrete purines and are cross-resistant to 8-azaadenine. They are recessive and represent a single complementation group, designated hpt1. Ade4-su, a prototrophic allele of ade4 with reduced activity of PRPPAT, is epistatic to hpt1, suppressing purine excretion and resistance to azaadenine but not resistance to azaguanine. The genotype ade2hpt1 does not respond to hypoxanthine. Hpt1 complements and is not closely linked to the purine excreting mutants pur1 to pur5. Hpt1 and pur6, a regultory mutant of PRPPAT, are also unlinked but do not complement, suggesting a protein-protein interaction between H:G-PRT and PRPPAT. Mycophenolic acid (MPA), an inhibitor of de novo guanine nucleotide synthesis, inhibits the growth of hpt1 and hpt1+. Xanthine allows both genotypes to grow in the presence of MPA whereas guanine only allows growth of hpt1+. Activity of A-PRT, X-PRT and H:G-PRT is present in hpt+. Hpt1 lacks activity of H:G-PRT but has normal A-PRT and X-PRT.
通过在携带从头嘌呤合成的第一种酶氨基磷酸核糖基转移酶（PRPPAT）的野生型等位基因ade4%的菌株中选择对8-氮鸟嘌呤的抗性，已分离出缺乏次黄嘌呤：鸟嘌呤磷酸核糖基转移酶（H:G-PRT）活性的酵母突变体。这些突变体排泄嘌呤，并且对8-氮腺嘌呤具有交叉抗性。它们是隐性的，代表一个单一的互补群，命名为hpt1。Ade4-su是ade4的一个原养型等位基因，其PRPPAT活性降低，对hpt1呈上位性，抑制嘌呤排泄和对氮腺嘌呤的抗性，但不抑制对氮鸟嘌呤的抗性。基因型ade2hpt1对次黄嘌呤无反应。Hpt1与嘌呤排泄突变体pur1至pur5互补且不紧密连锁。Hpt1和pur6（PRPPAT的一个调节突变体）也不连锁但不互补，这表明H:G-PRT和PRPPAT之间存在蛋白质-蛋白质相互作用。霉酚酸（MPA）是一种从头鸟嘌呤核苷酸合成的抑制剂，可抑制hpt1和hpt1+的生长。黄嘌呤使两种基因型在MPA存在下都能生长，而鸟嘌呤仅使hpt1+生长。hpt+中存在A-PRT、X-PRT和H:G-PRT的活性。Hpt1缺乏H:G-PRT的活性，但具有正常的A-PRT和X-PRT。
