title: Cdc14 targets the Holliday junction resolvase Yen1 to the nucleus in early anaphase.
abstract: The only canonical Holliday junction (HJ) resolvase identified in eukaryotes thus far is Yen1/GEN1. Nevertheless, Yen1/GEN1 appears to have a minor role in HJ resolution, and, instead, other structure-specific endonucleases (SSE) that recognize branched DNA play the leading roles, Mus81-Mms4/EME1 being the most important in budding yeast. Interestingly, cells tightly regulate the activity of each HJ resolvase during the yeast cell cycle. Thus, Mus81-Mms4 is activated in G 2/M, while Yen1 gets activated shortly afterwards. Nevertheless, cytological studies have shown that Yen1 is sequestered out of the nucleus when cyclin-dependent kinase activity is high, i.e., all of the cell cycle but G 1. We here show that the mitotic master phosphatase Cdc14 targets Yen1 to the nucleus in early anaphase through the FEAR network. We will further show that this FEAR-mediated Cdc14-driven event is sufficient to back-up Mus81-Mms4 in removing branched DNA structures, which are especially found in the long chromosome arms upon replication stress. Finally, we found that MEN-driven Cdc14 re-activation in late anaphase is essential to keep Yen1 in the nucleus until the next G 1. Our results highlight the essential role that early-activated Cdc14, i.e., through the FEAR network, has in removing all kind of non-proteinaceous linkages that preclude faithful sister chromatid segregation in anaphase. In addition, our results support the general idea of Yen1 acting as a last resource endonuclease to deal with any remaining HJ that might compromise genetic stability during chromosome segregation.
authors.affiliation: Genomic Instability & Cancer Group; Unidad de Investigación; Hospital Universitario Nuestra Señora de Candelaria; Santa Cruz de Tenerife, Spain.
authors.forename: Jonay
authors.initials: J
authors.lastname: García-Luis
authors.affiliation: Cell Cycle Group; MRC Clinical Sciences Centre; Imperial College London; London, UK.
authors.forename: Andrés
authors.initials: A
authors.lastname: Clemente-Blanco
authors.affiliation: Cell Cycle Group; MRC Clinical Sciences Centre; Imperial College London; London, UK.
authors.forename: Luis
authors.initials: L
authors.lastname: Aragón
authors.affiliation: Genomic Instability & Cancer Group; Unidad de Investigación; Hospital Universitario Nuestra Señora de Candelaria; Santa Cruz de Tenerife, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Machín
mesh_terms: D000705:Anaphase / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D004843:Epistasis, Genetic; D045585:Flap Endonucleases / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D045565:Holliday Junction Resolvases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D004720:Endonucleases; D045585:Flap Endonucleases; C411624:MUS81 protein, S cerevisiae; D045565:Holliday Junction Resolvases; C533749:Yen1 protein, S cerevisiae; C112337:MMS4 protein, S cerevisiae; D017027:Protein Tyrosine Phosphatases
keywords: Cdc14; Holliday junction; MMS; Mus81-Mms4; Saccharomyces cerevisiae; Yen1; anaphase