The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor
Ivanova, Tsvetomira ; Alves-Rodrigues, Isabel ; Gomez-Escoda, Blanca ; Dutta, Chaitali ; DeCaprio, James A. ; Rhind, Nicholas ; Hidalgo, Elena ; Ayte, Jose
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Keywords
CDC2 Protein Kinase
Cell Cycle Proteins
*DNA Damage
*DNA Replication
DNA, Fungal
G1 Phase Cell Cycle Checkpoints
Gene Expression Regulation, Fungal
Homeodomain Proteins
Mutation
Phosphorylation
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
Schizosaccharomyces
Schizosaccharomyces pombe Proteins
Transcription Factors
Cell Biology
Cellular and Molecular Physiology
Molecular Biology
Molecular Genetics
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Abstract
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.
Source
Mol Biol Cell. 2013 Nov;24(21):3350-7. doi: 10.1091/mbc.E13-05-0257. Epub 2013 Sep 4. Link to article on publisher's site