ArticleThe Journal of biological chemistry2014
A role for Saccharomyces cerevisiae Tpa1 protein in direct alkylation repair.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Fungal DNA damage repair: from model to driver of virulence and AMR.Bioscience reports · 2026Review
- Functional and comparative analysis of the FeBiology methods & protocols · 2025Article
- DNA adduct formation in Saccharomyces cerevisiae following exposure to environmental pollutants, as in vivo model for molecular toxicity studies.World journal of microbiology & biotechnology · 2024Article
- Interactions between HIV protease inhibitor ritonavir and human DNA repair enzyme ALKBH2: a molecular dynamics simulation study.Molecular diversity · 2023Article
- The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions.eLife · 2021Article
- Iron in Translation: From the Beginning to the End.Microorganisms · 2021Review
- Human RAD51 paralogue RAD51C fosters repair of alkylated DNA by interacting with the ALKBH3 demethylase.Nucleic acids research · 2019Article
- Expansion of base excision repair compensates for a lack of DNA repair by oxidative dealkylation in budding yeast.The Journal of biological chemistry · 2019Article
- Escherichia coli AlkB interacts with single-stranded DNA binding protein SSB by an intrinsically disordered region of SSB.Molecular biology reports · 2018Article
- Oxygen-responsive transcriptional regulation of lipid homeostasis in fungi: Implications for anti-fungal drug development.Seminars in cell & developmental biology · 2018Review
- RecA stimulates AlkB-mediated direct repair of DNA adducts.Nucleic acids research · 2016Article
- 2-Oxoglutarate-dependent dioxygenases are sensors of energy metabolism, oxygen availability, and iron homeostasis: potential role in the regulation of aging process.Cellular and molecular life sciences : CMLS · 2015Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alkylating agents induce cytotoxic DNA base adducts. In this work, we provide evidence to suggest, for the first time, that Saccharomyces cerevisiae Tpa1 protein is involved in DNA alkylation repair. Little is known about Tpa1 as a repair protein beyond the initial observation from a high-throughput analysis indicating that deletion of TPA1 causes methyl methane sulfonate sensitivity in S. cerevisiae. Using purified Tpa1, we demonstrate that Tpa1 repairs both single- and double-stranded methylated DNA. Tpa1 is a member of the Fe(II) and 2-oxoglutarate-dependent dioxygenase family, and we show that mutation of the amino acid residues involved in cofactor binding abolishes the Tpa1 DNA repair activity. Deletion of TPA1 along with the base excision repair pathway DNA glycosylase MAG1 renders the tpa1Δmag1Δ double mutant highly susceptible to methylation-induced toxicity. We further demonstrate that the trans-lesion synthesis DNA polymerase Polζ (REV3) plays a key role in tolerating DNA methyl-base lesions and that tpa1Δmag1revΔ3 triple mutant is extremely susceptible to methylation-induced toxicity. Our results indicate a synergism between the base excision repair pathway and direct alkylation repair by Tpa1 in S. cerevisiae. We conclude that Tpa1 is a hitherto unidentified DNA repair protein in yeast and that it plays a crucial role in reverting alkylated DNA base lesions and cytotoxicity.
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