Investigating Tangeretin Targeted Pathway by Chemical-Genetic Interaction in Yeast
Date Issued
2011
Date
2011
Author(s)
Yen Chong, Shin
Abstract
Polymethoxyflavones (PMFs) is a dietary phytochemical and they have been widely investigated in the field of inflammatory and anti-carcinogenic with proven bioactivities but they actual functioning target in cells remain unclear. Here, we used the model of chemical-genetic interaction model, with budding yeast as platform, to screen the potential targets or pathways involved by PMFs. We found out that SGS1 gene deleted yeast is sensitive to tangeretin, one of a member of PMFs. sgs1 defective yeast showed lower growth rate, survival rate, delayed G1 and S phase and elevated γH2A level in cell cycle under tryptophan drop-out condition. Through microarray, we found out that tangeretin is potential to inhibit expression of RNA progression related genes and up-regulated nitrogen compounds and amino acid synthesis pathways of sgs1 defective cells. Data also showed that tangeretin is incapable to inhibit protein synthesis directly as cycloheximide do. Interestingly, cycloheximide rescued the sensitive- phenotype of sgs1 and slx4 defective cells under tryptophan depletion and tangeretin involved condition. Our results showed tangeretin is potential to suppress rRNA precession of sgs1 defective cells and resulting improper protein synthesis under tryptophan depletion condition. This result demonstrated the potential pathway of anti-carcinogenic effect played by tangeretin. Additionally, we also observed the potential of availability of relationship between amino acid balances and DNA double strains break repair pathways. However, further investigation is required for this observation.
Subjects
yeast
polymethoxyflavones
tangeretin
chemical-gene interaction
Type
thesis
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