Co-ordinate Control of Synthesis of Mitochondrial and Non-mitochondrial Hemoproteins: a Binding Site for the HAP1 (CYP1) Protein in the UAS Region of the Yeast Catalase T Gene (CTT1)
Overview
Molecular Biology
Affiliations
Control of expression of the Saccharomyces cerevisiae CTT1 (catalase T) gene by the HAP1 (CYP1) gene, a mediator of heme control of mitochondrial cytochromes, was studied. Expression of a CTT1-lacZ fusion in a hap1 mutant showed that the CTT1 promoter is under HAP1 control. As demonstrated by a gel retardation assay, the HAP1 protein binds to a heme control region of the CTT1 gene. This binding in vitro is stimulated by hemin. The HAP1-binding sequence was localized by using DNA fragments spanning different regions, by DNase I footprinting and by methylation interference of DNA-protein binding. The binding site was compared to the HAP1-binding sequences previously characterized in detail (UAS1CYC1, UASCYC7). There is strikingly little similarity between the three sequences, which have only four of those 23 bp in common which are protected from DNase I digestion. However, the pattern of major and minor groove contacts in the complex is quite similar in all three cases. The results obtained show that there is true co-ordinate control of expression of mitochondrial cytochromes and at least some extra-mitochondrial hemoproteins. Heme acts as a metabolic signal in this coordination, which is mediated by the HAP1 protein.
Cillingova A, Toth R, Mojakova A, Zeman I, Vrzonova R, Sivakova B PLoS Genet. 2022; 18(3):e1009815.
PMID: 35255079 PMC: 8929692. DOI: 10.1371/journal.pgen.1009815.
Stuecker T, Scholes A, Lewis J PLoS Genet. 2018; 14(4):e1007335.
PMID: 29649251 PMC: 5978988. DOI: 10.1371/journal.pgen.1007335.
Extent of structural asymmetry in homodimeric proteins: prevalence and relevance.
Swapna L, Srikeerthana K, Srinivasan N PLoS One. 2012; 7(5):e36688.
PMID: 22629324 PMC: 3358323. DOI: 10.1371/journal.pone.0036688.
Correia M, Sinclair P, De Matteis F Drug Metab Rev. 2010; 43(1):1-26.
PMID: 20860521 PMC: 3034403. DOI: 10.3109/03602532.2010.515222.
Sulfiredoxin: a potential therapeutic agent?.
Findlay V, Tapiero H, Townsend D Biomed Pharmacother. 2005; 59(7):374-9.
PMID: 16102934 PMC: 6361122. DOI: 10.1016/j.biopha.2005.07.003.