title: Inhibition of the mitotic exit network in response to damaged telomeres.
abstract: When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa/Departamento de Genética, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Valerio-Santiago
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: de Los Santos-Velázquez
authors.forename: Fernando
authors.initials: F
authors.lastname: Monje-Casas
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D064447:Checkpoint Kinase 2 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D008938:Mitosis; D010766:Phosphorylation / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics; D016615:Telomere / Q000235:genetics*
chemical_list: C119117:BFA1 protein, S cerevisiae; C070351:BUB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae