title: The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor.
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.
authors.affiliation: Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, Barcelona 08003, Spain Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: Tsvetomira
authors.initials: T
authors.lastname: Ivanova
authors.forename: Isabel
authors.initials: I
authors.lastname: Alves-Rodrigues
authors.forename: Blanca
authors.initials: B
authors.lastname: Gómez-Escoda
authors.forename: Chaitali
authors.initials: C
authors.lastname: Dutta
authors.forename: James A
authors.initials: JA
authors.lastname: DeCaprio
authors.forename: Nick
authors.initials: N
authors.lastname: Rhind
authors.forename: Elena
authors.initials: E
authors.lastname: Hidalgo
authors.forename: José
authors.initials: J
authors.lastname: Ayté
mesh_terms: D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; C489911:DSC1 protein, S pombe; D018398:Homeodomain Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C545558:Yox1 protein, S pombe; C061178:cdc10 protein, S pombe; D016203:CDC2 Protein Kinase