DNA damage is an ongoing threat to both the ability of the cell to faithfully transmit genetic information to its offspring as well as to its own survival. In order to maintain genomic integrity, eukaryotes have developed a highly conserved mechanism to detect, signal and repair damage in DNA, known as the DNA damage response (DDR). In fission yeast the two DDR pathways converge at the regulation of single transcriptional factor complex (MBF) resulting in opposite directions. We have shown that when the DNA-synthesis checkpoint is activated, Max1 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. In contrast, upon DNA damage, Chk1 the effector kinase of DNA damage checkpoint is activated and blocks the cell cycle progression, inducing DNA repair and repressing the MBF dependent transcription. We have revealed that Cdc10 is the target of the DNA-damage checkpoint and when cells are treated with MMS or are exposed to IR, Chk1 phosphorylates Cdc10 inducing the exit of MBF from chromatin. The consequence is that under these conditions, MBF-dependent transcription is repressed. Thus, Max1 and Cdc10 couple normal cell cycle regulation and the DNA-synthesis and DNA-damage checkpoints into MBF.

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, stabilizing stalled replication forks and triggering transcriptional activation of S-phase genes; the molecular basis of this last effect remains largely unknown. The MBF complex controls the transcription of S-phase genes. We have purified novel interactors of the MBF complex and among them we have identified the repressor Max1. When the DNA synthesis checkpoint is activated, Max1 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 this challenge. / Cuando la replicación del DNA se ve alterada, las células activan un mecanismo de control bloqueando la progresión del ciclo celular hasta que son capaces de superar el daño. En la levadura de fisión, Cds1 es la proteína kinasa efectora de dicha respuesta, mediante inhibición de la entrada en fase M, estabilización las horquillas de replicación bloqueadas, e inducción de la activación de la transcripción de los genes de fase S; siendo la base molecular de este último proceso poco conocida. El factor de transcripción MBF controla la transcripción de los genes de fase S. Hemos purificado proteínas que interaccionan con MBF, y entre ellas, hemos identificado al represor Max1. Cuando el checkpoint de síntesis de DNA es activado, Max1 es fosforilado por la kinasa Cds1, y esto se traduce en la disociación de Max1 del complejo MBF. Como consecuencia, la transcripción MBF-dependiente se mantiene activa hasta que las células son capaces de superar el daño.