Phosphorylation of the Cohesin Subunit Scc1 by Polo/Cdc5 Kinase Regulates Sister Chromatid Separation in Yeast

Alexandru, Gabriela; Uhlmann, Frank; Mechtler, Karl; Poupart, Marc‐André; Nasmyth, Kim

doi:10.1016/s0092-8674(01)00362-2

Cited by 334 publications

(325 citation statements)

References 53 publications

(2 reference statements)

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“…In contrast to vertebrate cells, which remove chromatinbound cohesin in a two-step fashion, yeast cells remove cohesin in one step through separase-mediated cleavage. During cohesin displacement in S. cerevisiae, the cohesin subunit SCC1 is phosphorylated by the Polo-homolog Cdc5 (Alexandru et al, 2001). This phosphorylation event strongly enhances SCC1-cleavage by separase and is essential for proper chromosome segregation.…”

Section: Plk1 and Condensation/separation Of Chromosomesmentioning

confidence: 99%

Getting in and out of mitosis with Polo-like kinase-1

2005

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Section: Plk1 and Condensation/separation Of Chromosomesmentioning

confidence: 99%

Getting in and out of mitosis with Polo-like kinase-1

2005

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“…Also it phosphorylates cohesin Scc1 and facilitates its cleavage by the separase Esp1 (Alexandru et al, 2001). The lethality in cdc5-1 mutants caused by the overexpression of PP2A subunits may result from the negative effects of PP2A on mitotic exit or on other Cdc5 related cell cycle processes.…”

Section: Genetic Screen For Genes Lethal To Cdc5-1 When Overexpressedmentioning

confidence: 99%

Phosphatase 2A Negatively Regulates Mitotic Exit inSaccharomyces cerevisiae

Wang

2006

MBoC

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In budding yeast Saccharomyces cerevisiae, Cdc5 kinase is a component of mitotic exit network (MEN), which inactivates cyclin-dependent kinase (CDK) after chromosome segregation. cdc5-1 mutants arrest at telophase at the nonpermissive temperature due to the failure of CDK inactivation. To identify more negative regulators of MEN, we carried out a genetic screen for genes that are toxic to cdc5-1 mutants when overexpressed. Genes that encode the B-regulatory subunit (Cdc55) and the three catalytic subunits (Pph21, Pph22, and Pph3) of phosphatase 2A (PP2A) were isolated. In addition to cdc5-1, overexpression of CDC55, PPH21, or PPH22 is also toxic to other temperature-sensitive mutants that display defects in mitotic exit. Consistently, deletion of CDC55 partially suppresses the temperature sensitivity of these mutants. Moreover, in the presence of spindle damage, PP2A mutants display nuclear localized Cdc14, the key player in MEN pathway, indicative of MEN activation. All the evidence suggests the negative role of PP2A in mitotic exit. Finally, our genetic and biochemical data suggest that PP2A regulates the phosphorylation of Tem1, which acts at the very top of MEN pathway. INTRODUCTIONThe key driving force for cell division in all eukaryotic cells is the conserved cyclin-dependent kinase (CDK). CDK activity fluctuates during the cell cycle, peaking at the S and M phases and dropping at the G1 phase. Although the high CDK activity is required for DNA duplication and chromosome segregation, the low CDK activity at late M and G1 phase is essential for the loading of DNA replication complexes onto replication origins (Noton and Diffley, 2000;Lengronne and Schwob, 2002). Thus, cells have developed a signal transduction pathway, named the mitotic exit network (MEN), to inactivate CDK after mitosis (Morgan, 1999). The components of the MEN pathway include protein kinases Cdc5, Cdc15, Dbf2, a GTPase Tem1, a phosphatase Cdc14, and a Dbf2 binding protein Mob1 Luca and Winey, 1998;Lee et al., 2001a). Phosphatase Cdc14, the key player in the MEN pathway, dephosphorylates Cdh1, an activator for APC (anaphase promoting complex), and subsequently activates the degradation of a Btype cyclin, Clb2. Cdc14 also enhances the stability of Sic1 protein, which acts as a CDK inhibitor (Visintin et al., 1998). During most of the cell cycle, Cdc14 is localized in the nucleolus, but its translocation out of the nucleolus in anaphase and telophase allows it to encounter its substrates, such as Cdh1 and Sic1. All the components in the MEN pathway are required for the release of Cdc14 from the nucleolus, suggesting that Cdc14 acts downstream of MEN pathway (Shou et al., 1999;Visintin et al., 1999).The regulation of MEN activity is achieved through the multilayer control of Tem1, a small GTPase that localizes at the spindle pole body (SPB) and acts on the very top of the MEN pathway. Tem1's activator, the GTPase exchange factor (GEF) Lte1, exhibits daughter-cell specific localization. Thus, SPB-localized Tem1 is activated after it encounters...

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“…The many functions of Plk1 at mitosis [87] are well accounted for by the variety of substrates so far identified for this kinase. These consist of proteins involved with chromosome segregation, such as cohesin [88], microtubules dynamics [89] and nucleation [90] as well as cytokinesis [91]. In addition to the regulation of mechanistic aspects of mitosis, Plk1 contributes to set the timing of entry and transition through mitosis by phosphorylating APC/C subunits [92,93].…”

Section: Polo-like Kinasementioning

confidence: 99%

Protein kinases controlling the onset of mitosis

Ferrari

2006

Cell. Mol. Life Sci.

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Abstract. This review article focuses on protein kinases regulating the onset and transition through mitosis. The essay begins by introducing the structural features of the protein kinase catalytic domain and emphasizing the mechanism of enzymatic activation of this class of proteins. Next follows a short historical perspective on cell division and a description of our current understanding of mitosis. In the central part of the review I examine the four major kinases that set the stage for mitosis, which

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Phosphorylation of the Cohesin Subunit Scc1 by Polo/Cdc5 Kinase Regulates Sister Chromatid Separation in Yeast

Cited by 334 publications

References 53 publications

Getting in and out of mitosis with Polo-like kinase-1

Getting in and out of mitosis with Polo-like kinase-1

Phosphatase 2A Negatively Regulates Mitotic Exit inSaccharomyces cerevisiae

Protein kinases controlling the onset of mitosis

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