Rdp1, a novel zinc finger protein, regulates the DNA damage response of rhp51(+) from Schizosaccharomyces pombe.
The Schizosaccharomyces pombe DNA repair gene rhp51(+) encodes a RecA-like protein with the DNA-dependent ATPase activity required for homologous recombination. The level of the rhp51(+) transcript is increased by a variety of DNA-damaging agents. Its promoter has two cis-acting DNA damage-responsive elements (DREs) responsible for DNA damage inducibility. Here we ... report identification of Rdp1, which regulates rhp51(+) expression through the DRE of rhp51(+). The protein contains a zinc finger and a polyalanine tract similar to ones previously implicated in DNA binding and transactivation or repression, respectively. In vitro footprinting and competitive binding assays indicate that the core consensus sequences (NGG/TTG/A) of DRE are crucial for the binding of Rdp1. Mutations of both DRE1 and DRE2 affected the damage-induced expression of rhp51(+), indicating that both DREs are required for transcriptional activation. In addition, mutations in the DREs significantly reduced survival rates after exposure to DNA-damaging agents, demonstrating that the damage response of rhp51(+) enhances the cellular repair capacity. Surprisingly, haploid cells containing a complete rdp1 deletion could not be recovered, indicating that rdp1(+) is essential for cell viability and implying the existence of other target genes. Furthermore, the DNA damage-dependent expression of rhp51(+) was significantly reduced in checkpoint mutants, raising the possibility that Rdp1 may mediate damage checkpoint-dependent transcription of rhp51(+).
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Sequence, Base Sequence, Binding Sites, Binding, Competitive, DNA Damage, DNA Repair, DNA-Binding Proteins, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Drug Resistance, Microbial, Fungal Proteins, Gene Expression Regulation, Fungal, Methyl Methanesulfonate, Molecular Sequence Data, Protein Binding, Rad51 Recombinase, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Homology, Amino Acid, Transcription, Genetic, Ultraviolet Rays, Zinc Fingers
Adenosine Triphosphatases, Amino Acid Sequence, Base Sequence, Binding Sites, Binding, Competitive, DNA Damage, DNA Repair, DNA-Binding Proteins, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Drug Resistance, Microbial, Fungal Proteins, Gene Expression Regulation, Fungal, Methyl Methanesulfonate, Molecular Sequence Data, Protein Binding, Rad51 Recombinase, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Homology, Amino Acid, Transcription, Genetic, Ultraviolet Rays, Zinc Fingers
Mol. Cell. Biol.
Date: Dec. 01, 2000
PubMed ID: 11073995
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