Analysis of pyrimidine catabolism in Drosophila melanogaster using epistatic interactions with mutations of pyrimidine biosynthesis and β-alanine metabolism
Analysis of pyrimidine catabolism in Drosophila melanogaster using epistatic interactions with mutations of pyrimidine biosynthesis and β-alanine metabolism
复制标题
DOI：
10.1534/genetics.105.052753
复制
发表时间：
2006-03-01
期刊：
影响因子：
3.3
通讯作者：
Rawls, JM
中科院分区：
文献类型：
--
作者：
Rawls, JM
嘧啶分解代谢的生化途径将嘧啶生物合成和补救途径与β-丙氨酸代谢联系起来，提供了一系列上位相互作用，可用于分析这些途径的突变。每种嘧啶分解代谢酶的功能丧失突变均已被鉴定和表征：二氢嘧啶脱氢酶 (DPD)、su(r) 突变体；二氢嘧啶酶 (DHP)、CRMP 突变体； β-丙氨酸合酶 (β AS)，pyd3 突变体。对于所有三个基因，突变体都是可行且可育的，除了各种上位相互作用之外，没有表现出明显的表型。所有三个基因的突变都会破坏黑色突变体深色角质层表型的基本功能获得性突变（r(Su(b))）的抑制，其中β-丙氨酸池减少；这些结果证实嘧啶是角质层色素沉着中β-丙氨酸的主要来源。基本突变体的截短翅表型被su(r)突变完全抑制，并被CRMP突变部分抑制；然而，pyd3 突变并未表现出抑制作用。类似地，sit(r) 突变体对膳食 5-氟尿嘧啶过敏，CRMP 突变体敏感性较低，pyd3 突变体表现出野生型敏感性。这些结果是在人类 5-氟嘧啶毒性和嘧啶分解代谢突变的类似后果的背景下讨论的。
The biochemical pathway for pyrimidine catabolism links the pathways for pyrimidine biosynthesis and salvage with beta-alanine metabolism, providing an array of epistatic interactions with which to analyze mutations of these pathways. Loss-of-function mutations have been identified and characterized for each of the enzymes for pyrimidine catabolism: dihydropyrimidine dehydrogenase (DPD), su(r) mutants; dihydropyrimidinase (DHP), CRMP mutants; beta-alanine synthase (beta AS), pyd3 mutants. For all three genes, mutants are viable and fertile and manifest no obvious phenotypes, aside from a variety of epistatic interactions. Mutations of all three genes disrupt suppression by the rudimentary gain-of-function mutation (r(Su(b))) of the dark cuticle phenotype of black mutants in which beta-alanine pools are diminished; these results confirm that pyrimidines are the major source of beta-alanine in cuticle pigmentation. The truncated wing phenotype of rudimentaty mutants is suppressed completely by su(r) mutations and partially by CRMP mutations; however, no Suppression is exhibited by pyd3 mutations. Similarly, sit(r) mutants are hypersensitive to dietary 5-fluorouracil, CRMP mutants are less sensitive, and pyd3 mutants exhibit wild-type sensitivity These results are discussed in the context of similar consequences of 5-fluoropyrimidine toxicity and pyrimidine catabolism mutations in humans.