The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor
Copyright policy )The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor
In fission yeast cells, Cds1 is the effector kinase of the DNA replication checkpoint. We previously showed that when the DNA replication checkpoint is activated, the repressor Yox1 is phosphorylated and inactivated by Cds1, resulting in activation of MluI-binding factor (MBF)–dependent transcription. This is essential to reinitiate DNA synthesis and for correct G1-to-S transition. Here we show that Cdc10, which is an essential part of the MBF core, is the target of the DNA damage checkpoint. When fission yeast cells are treated with DNA-damaging agents, Chk1 is activated and phosphorylates Cdc10 at its carboxy-terminal domain. This modification is responsible for the repression of MBF-dependent transcription through induced release of MBF from chromatin. This inactivation of MBF is important for survival of cells challenged with DNA-damaging agents. Thus Yox1 and Cdc10 couple normal cell cycle regulation in unperturbed conditions and the DNA replication and DNA damage checkpoints into a single transcriptional complex.
- Harvard University United States
- Universitat Pompeu Fabra Spain
- University of Massachusetts Medical School United States
- Dana-Farber Cancer Institute United States
DNA Replication, 570, ADN, Blotting, Western, *DNA Damage, 610, Cell Cycle Proteins, *DNA Replication, Molecular Genetics, Gene Expression Regulation, Fungal, CDC2 Protein Kinase, Schizosaccharomyces, Phosphorylation, DNA, Fungal, Molecular Biology, Homeodomain Proteins, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Proteïnes quinases -- Metabolisme, Schizosaccharomyces pombe -- Metabolisme, DNA, Cell Biology, Articles, G1 Phase Cell Cycle Checkpoints, Cellular and Molecular Physiology, Fungal, Gene Expression Regulation, Mutation, Schizosaccharomyces pombe Proteins, Western, DNA Damage, Protein Binding, Transcription Factors
DNA Replication, 570, ADN, Blotting, Western, *DNA Damage, 610, Cell Cycle Proteins, *DNA Replication, Molecular Genetics, Gene Expression Regulation, Fungal, CDC2 Protein Kinase, Schizosaccharomyces, Phosphorylation, DNA, Fungal, Molecular Biology, Homeodomain Proteins, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Proteïnes quinases -- Metabolisme, Schizosaccharomyces pombe -- Metabolisme, DNA, Cell Biology, Articles, G1 Phase Cell Cycle Checkpoints, Cellular and Molecular Physiology, Fungal, Gene Expression Regulation, Mutation, Schizosaccharomyces pombe Proteins, Western, DNA Damage, Protein Binding, Transcription Factors
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