Loss of APD1 in Yeast Confers Hydroxyurea Sensitivity Suppressed by Yap1p Transcription Factor

Hei Man Vincent Tang, Kewu Pan, Ka Yiu Edwin Kong, Ligang Hu, Ling Chim Chan, Kam Leung Siu, Hongzhe Sun, Chi Ming Wong, Dong Yan Jin

Research output: Journal article publicationJournal articleAcademic researchpeer-review

11 Citations (Scopus)


Ferredoxins are iron-sulfur proteins that play important roles in electron transport and redox homeostasis. Yeast Apd1p is a novel member of the family of thioredoxin-like ferredoxins. In this study, we characterized the hydroxyurea (HU)-hypersensitive phenotype of apd1Î " cells. HU is an inhibitor of DNA synthesis, a cellular stressor and an anticancer agent. Although the loss of APD1 did not influence cell proliferation or cell cycle progression, it resulted in HU sensitivity. This sensitivity was reverted in the presence of antioxidant N-acetyl-cysteine, implicating a role for intracellular redox. Mutation of the iron-binding motifs in Apd1p abrogated its ability to rescue HU sensitivity in apd1 " cells. The iron-binding activity of Apd1p was verified by a color assay. By mass spectrometry two irons were found to be incorporated into one Apd1p protein molecule. Surprisingly, ribonucleotide reductase genes were not induced in apd1Î " cells and the HU sensitivity was unaffected when dNTP production was boosted. A suppressor screen was performed and the expression of stress-regulated transcription factor Yap1p was found to effectively rescue the HU sensitivity in apd1Î " cells. Taken together, our work identified Apd1p as a new ferredoxin which serves critical roles in cellular defense against HU.
Original languageEnglish
Article number7897
JournalScientific Reports
Publication statusPublished - 20 Jan 2015
Externally publishedYes

ASJC Scopus subject areas

  • General


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