The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains.
AUTOR(ES)
Xanthoudakis, S
RESUMO
The DNA binding activity of transcription factor AP-1 is regulated in vitro by a posttranslational mechanism involving reduction/oxidation (redox). Redox regulation is mediated by a conserved cysteine residue in the DNA-binding domain of Fos and Jun. Previously, we demonstrated that a DNA repair protein, Ref-1, could stimulate the DNA binding activity of Fos-Jun dimers by reducing this cysteine residue. To examine the relationship between the redox and repair functions of Ref-1, we generated a series of deletion mutants. Analysis of the truncated proteins in vitro revealed that the redox and repair activities are encoded by distinct regions of Ref-1. Sequences in the N-terminal domain of Ref-1 that are not present in functionally related proteins from other organisms are required for the redox activity, whereas the DNA repair activity requires conserved C-terminal sequences. Chemical alkylation or oxidation of cysteine sulfhydryls inhibits the redox activity of Ref-1 without affecting its DNA repair activity. Crosslinking studies suggest that a direct cysteine-mediated interaction occurs between Ref-1 and Jun.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=42878Documentos Relacionados
- Suppression of human DNA alkylation-repair defects by Escherichia coli DNA-repair genes.
- Quantitative Implications of the DNA-Repair Model of Gene Conversion
- Screening the yeast genome for new DNA-repair genes
- Cysteine 64 of Ref-1 Is Not Essential for Redox Regulation of AP-1 DNA Binding
- Dhr6, a Drosophila homolog of the yeast DNA-repair gene RAD6.
