title: G1/S transcription and the DNA synthesis checkpoint: common regulatory mechanisms.
abstract: When DNA replication is challenged, cells activate a DNA-synthesis checkpoint blocking cell cycle progression until they are able to overcome the replication defects. In fission yeast, Cds1 is the effector kinase of this checkpoint, inhibiting M phase entry through inactivation of the phosphatase Cdc25, stabilizing stalled replication forks to prevent deleterious DNA structures and triggering transcriptional activation of S-phase genes. The MBF complex controls the transcription of genes required for the S phase and Yox1, a homeodomain-containing protein, binds and represses MBF-dependent transcription at the end of S phase in a cell cycle-regulated manner. Interestingly, when the DNA synthesis checkpoint is activated, Yox1 is phosphorylated by Cds1 resulting in the abrogation of its binding to MBF. As a consequence, MBF-dependent transcription is maintained active until cells are able to overcome the replication challenge. Thus, Yox1 couples normal cell cycle regulation and the DNA synthesis checkpoint in a single transcriptional complex.
authors.affiliation: Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Tsvetomira
authors.initials: T
authors.lastname: Ivanova
authors.forename: Blanca
authors.initials: B
authors.lastname: Gómez-Escoda
authors.forename: Elena
authors.initials: E
authors.lastname: Hidalgo
authors.forename: José
authors.initials: J
authors.lastname: Ayté
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004247:DNA / Q000096:biosynthesis*; D004261:DNA Replication; D016193:G1 Phase / Q000235:genetics*; D018398:Homeodomain Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016196:S Phase / Q000235:genetics*; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C489911:DSC1 protein, S pombe; D018398:Homeodomain Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C545558:Yox1 protein, S pombe; D004247:DNA; D064447:Checkpoint Kinase 2; C578636:Cds1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D020687:cdc25 Phosphatases