Dual role for the yeast THI4 gene in thiamine biosynthesis and DNA damage tolerance

Machado, Carlos Renato; Um, Praekelt; Rc, de Oliveira; Ac, Barbosa; Kl, Byrne; Pa, Meacock; Menck, Carlos Frederico Martins

doi:10.1006/jmbi.1997.1302

Cited by 93 publications

(91 citation statements)

References 32 publications

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“…The most highly represented cluster, MD249100, is very closely related to THI4, an Arabidopsis gene that participates in thiamine synthesis (Machado et al, 1997). Another representative of this highly represented group is MD176720, corresponding to a protein included in the glycoside hydrolase family 16 (GH16), which contains members with diverse (Henrissat and Bairoch, 1993; http://afmb.cnrs-mrs.fr/CAZY).…”

Section: Identification Of Genes Potentially Highly Expressed In Fruitmentioning

confidence: 99%

Identification of Genes with Potential Roles in Apple Fruit Development and Biochemistry through Large-Scale Statistical Analysis of Expressed Sequence Tags

Sugimoto²,

et al. 2006

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Advanced studies of apple (Malus domestica Borkh) development, physiology, and biochemistry have been hampered by the lack of appropriate genomics tools. One exception is the recent acquisition of extensive expressed sequence tag (EST) data. The entire available EST dataset for apple resulted from the efforts of at least 20 contributors and was derived from more than 70 cDNA libraries representing diverse transcriptional profiles from a variety of organs, fruit parts, developmental stages, biotic and abiotic stresses, and from at least nine cultivars. We analyzed apple EST sequences available in public databanks using statistical algorithms to identify those apple genes that are likely to be highly expressed in fruit, expressed uniquely or preferentially in fruit, and/or temporally or spatially regulated during fruit growth and development. We applied these results to the analysis of biochemical pathways involved in biosynthesis of precursors for volatile esters and identified a subset of apple genes that may participate in generating flavor and aroma components found in mature fruit.Cultivated apple (Malus domestica Borkh) is among the most diverse and ubiquitously cultivated fruit species. Apple is a member of the Rosaceae family, which includes many commercial fruit (e

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Section: Identification Of Genes Potentially Highly Expressed In Fruitmentioning

confidence: 99%

Identification of Genes with Potential Roles in Apple Fruit Development and Biochemistry through Large-Scale Statistical Analysis of Expressed Sequence Tags

Sugimoto²,

et al. 2006

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“…in the biosynthesis of thiamine (vitamin B1) and may be involved in protection against organellar DNA damage (Machado et al, 1996;Machado et al, 1997). The mature THI1 protein is synthesized with a typical N-terminal chloroplastic transit peptide, which is in agreement with the plastid location for the pathway (Belanger et al, 1995).…”

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confidence: 90%

Differential usage of two in-frame translational start codons regulates subcellular localization ofArabidopsis thalianaTHI1

Chabregas

Luche

Sluys

et al. 2003

Journal of Cell Science

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Arabidopsis thaliana THI1 is encoded by a single nuclear gene and directed simultaneously to mitochondria and chloroplasts from a single major transcript. In vitro transcription/translation experiments revealed the presence of two translational products by the differential usage of two in-frame translational start codons. The coupling site-specific mutations on the THI1 encoding sequence with green fluorescent protein (GFP) gene fusions showed that translation initiation at the first AUG directs translocation of THI1 to chloroplasts. However, when translation starts from the second AUG, THI1 is addressed to mitochondria. Analysis of the translation efficiency of thi1 mRNA revealed that the best context for translation initiation is to use the first AUG. In addition, a suboptimal context in the vicinity of the second AUG initiation codon, next to a stable stem-and-loop structure that is likely to slow translation, has been noted. The fact that translation preferentially occurs in the first AUG of this protein suggests a high requirement for TH1 in chloroplasts. Although the frequency of upstream AUG translation is higher, according to the first AUG rule, initiation at the second AUG deviates significantly from Kozak's consensus. It suggests leaky ribosomal scanning, reinitiation or the internal entry of ribosomes to assure mitochondrial protein import.

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“…SOD2 is a known target of HapI and HapII/3/4/5 and is also known to be regulated in a heme-dependent manner (29). Down-regulation of Thi4, which has a role in thiamine biosynthesis as well as in mitochondrial DNA maintenance (30), might indicate that a defect in respiration could cause mitochondrial genome instability. Four DNA repair genes were also found to be significantly up-regulated (supplemental Table S1) thus supporting this hypothesis.…”

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confidence: 99%

Hap4 Is Not Essential for Activation of Respiration at Low Specific Growth Rates in Saccharomyces cerevisiae

Raghevendran

Patil

Olsson

et al. 2006

Journal of Biological Chemistry

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In Saccharomyces cerevisiae, the heme-activated protein complex Hap2/3/4/5 plays a major role in the transcription of genes involved in respiration. Thus, overexpression of HAP4 has been shown to result in a 10% increase in the respiratory capacity. Here the physiology of a HAP4-deleted S. cerevisiae strain was investigated, and we found that the hap4⌬ S. cerevisiae exhibited poor growth on ethanol, although the growth rate on glucose was indifferent from the wild type in aerobic as well as anaerobic cultures. Moreover, it exhibited a large (75%) reduction in the critical glucose uptake rate at which fermentative metabolism is onset, indicating a substantial reduction in respiratory capacity. We also performed whole genome transcription analysis for the hap4⌬ and the wild type, grown in carbonlimited chemostat cultures operated at a dilution rate of 0.05 h ؊1 .Although both strains exhibited respiratory metabolism, there was significant change in expression of many genes in the hap4⌬ strain. These genes are involved in several different parts of the metabolism, including oxidative stress response, peroxisomal functions, and energy generation. This study strongly indicates that Hap4 activation only occurs at intermediate specific growth rates, below which the transcription of genes responsible for respiration is dependent on the Hap2/3/5 complex and above which the Hap4 protein augments the transcription. Furthermore, statistical analysis of the transcription data and integration of the data with a genome scale metabolic network provided new insight and evidence for the role of Hap4 in transcriptional regulation of mitochondrial respiration.Respiration plays a central role in providing Gibbs free energy required for growth and overall cellular function. The respiratory chain is closely coupled with the operation of the tricarboxylic acid cycle as it ensures oxidation of NADH generated in this cycle. Proper functioning of respiration is therefore essential not only for providing Gibbs free energy but also for operation of the tricarboxylic acid cycle. Consequently, many metabolic diseases result either directly or indirectly from altered functioning of respiration. Moreover, respiration and energy metabolism are of particular interest in metabolic engineering, where the objective may be to design new cell factories for production of chemicals that demand energy for their synthesis. The yeast Saccharomyces cerevisiae is not only an important cell factory for production of fuels, chemicals, and pharmaceuticals but also serves as an important eukaryotic model organism for studying human diseases, thus making it an attractive model for studying respiration.In S. cerevisiae, the heme-activated protein complex Hap2/3/4/5 plays a major role in orchestrating the transcription of genes involved in the tricarboxylic acid cycle, the electron transport chain, ATP generation, and mitochondrial biogenesis by binding to the CCAAT box at the upstream activation sequence of genes encoding enzymes of these pathways (1). Binding is ...

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Dual role for the yeast THI4 gene in thiamine biosynthesis and DNA damage tolerance

Cited by 93 publications

References 32 publications

Identification of Genes with Potential Roles in Apple Fruit Development and Biochemistry through Large-Scale Statistical Analysis of Expressed Sequence Tags

Identification of Genes with Potential Roles in Apple Fruit Development and Biochemistry through Large-Scale Statistical Analysis of Expressed Sequence Tags

Differential usage of two in-frame translational start codons regulates subcellular localization ofArabidopsis thalianaTHI1

Hap4 Is Not Essential for Activation of Respiration at Low Specific Growth Rates in Saccharomyces cerevisiae

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