Interpreting spatial information and regulating mitosis in response to spindle orientation: Figure 1.

Burke, Daniel J.

doi:10.1101/gad.1826409

Cited by 8 publications

(9 citation statements)

References 42 publications

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“…First, like Mad2, it is required to prevent Pds1 degradation; second, it antagonizes Net1 phosphorylation, through which it is thought to prevent FEAR [ 14 , 15 ]. The Bub2-dependent spindle orientation checkpoint inhibits Cdc14 release by MEN and prevents metaphase, anaphase and mitotic exit [ 15 , 22 ]. Therefore, while wild-type cells arrest at metaphase in response to nocodazole, mad2Δ mutant cells pass through metaphase, cdc55Δ cells pass through metaphase and FEAR, and bub2Δ cells pass through metaphase, anaphase and mitotic exit.…”

Section: Resultsmentioning

confidence: 99%

“…More recent findings challenge this model by demonstrating that Esp1 contributes to mitotic exit primarily through the destruction of sister chromatid cohesion in a manner that requires mitotic spindle activity [ 21 ]. It appears, therefore, that Esp1 might activate mitotic exit by permitting spindle growth and spindle pole translocation into the daughter bud, a potential mechanism for activation of the MEN [ 22 ]. Additional recent work indicates that Zds1 and Zds2 downregulate PP2A Cdc55 by stimulating the nuclear export of Cdc55, allowing Net1 phosphorylation to accumulate [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, some studies of Esp1, Zds1 or Zds2 overexpression show Cdc14 being released to both the nucleus and cytoplasm [ 17 , 18 ]. Export from the nucleus would allow Cdc14 access to mitotic exit regulators such as Swi5, Cdh1 and Cdc15 in the cytoplasm, at the bud neck or on the cytoplasmic face of the spindle pole [ 22 , 25 – 28 ]. Therefore, it would be useful to know whether the FEAR pathway can stimulate nuclear export of Cdc14.…”

Section: Introductionmentioning

confidence: 99%

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Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit

Yellman

Roeder

2015

PLoS ONE

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Cdc14 phosphatase is a key regulator of exit from mitosis, acting primarily through antagonism of cyclin-dependent kinase, and is also thought to be important for meiosis. Cdc14 is released from its sequestration site in the nucleolus in two stages, first by the non-essential Cdc Fourteen Early Anaphase Release (FEAR) pathway and later by the essential Mitotic Exit Network (MEN), which drives efficient export of Cdc14 to the cytoplasm. We find that Cdc14 is confined to the nucleus during early mitotic anaphase release, and during its meiosis I release. Proteins whose degradation is directed by Cdc14 as a requirement for mitotic exit (e.g. the B-type cyclin, Clb2), remain stable during mitotic FEAR, a result consistent with Cdc14 being restricted to the nucleus and not participating directly in mitotic exit. Cdc14 released by the FEAR pathway has been proposed to have a wide variety of activities, all of which are thought to promote passage through anaphase. Proposed functions of FEAR include stabilization of anaphase spindles, resolution of the rDNA to allow its segregation, and priming of the MEN so that mitotic exit can occur promptly and efficiently. We tested the model for FEAR functions using the FEAR-deficient mutation net1-6cdk. Our cytological observations indicate that, contrary to the current model, FEAR is fully dispensable for timely progression through a series of anaphase landmarks and mitotic exit, although it is required for timely rDNA segregation. The net1-6cdk mutation suppresses temperature-sensitive mutations in MEN genes, suggesting that rather than activating mitotic exit, FEAR either inhibits the MEN or has no direct effect upon it. One interpretation of this result is that FEAR delays MEN activation to ensure that rDNA segregation occurs before mitotic exit. Our findings clarify the distinction between FEAR and MEN-dependent Cdc14 activities and will help guide emerging quantitative models of this cell cycle transition.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit

Yellman

Roeder

2015

PLoS ONE

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“…Indeed, we recently demonstrated the presence of such a checkpoint by showing that GSCs mutant for the centrosomin ( cnn ) gene or those overexpressing a dominant-negative form of E-cadherin fail to delay the cell cycle even when centrosomes are misoriented (Inaba et al, 2010). The surveillance mechanism that coordinates the position of the spindle and cell cycle progression is best understood as the spindle position checkpoint (SPOC) in budding yeast (Burke, 2009). The SPOC inhibits the mitotic exit network (MEN) when the spindle is mispositioned within the mother cell.…”

Section: Introductionmentioning

confidence: 99%

Regulation of cyclin A localization downstream of Par-1 function is critical for the centrosome orientation checkpoint in Drosophila male germline stem cells

Yuan

Chiang

Cheng

et al. 2012

Developmental Biology

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Male germline stem cells (GSCs) in Drosophila melanogaster divide asymmetrically by orienting mitotic spindle with respect to the niche, a microenvironment that specifies stem cell identity. The spindle orientation is prepared during interphase through stereotypical positioning of the centrosomes. We recently demonstrated that GSCs possess a checkpoint (“the centrosome orientation checkpoint”) that monitors correct centrosome orientation prior to mitosis to ensure an oriented spindle and thus asymmetric outcome of the division. Here, we show that Par-1, a serine/threonine kinase that regulates polarity in many systems, is involved in this checkpoint. Par-1 shows a cell cycle-dependent localization to the spectrosome, a germline-specific, endoplasmic reticulum-like organelle. Furthermore, the localization of cyclin A, which is normally localized to the spectrosome, is perturbed in par-1 mutant GSCs. Interestingly, overexpression of mutant cyclin A that does not localize to the spectrosome and mutation in hts, a core component of the spectrosome, both lead to defects in the centrosome orientation checkpoint. We propose that the regulation of cyclin A localization via Par-1 function plays a critical role in the centrosome orientation checkpoint.

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“…In addition to such elaborate cellular mechanisms that position centrosomes and orient spindles, male GSCs may possess a checkpoint that monitors the correct centrosome orientation prior to commitment to mitosis [45]. Such a mechanism could be similar to spindle position checkpoint (SPOC) observed in S. cerevisiae [58]. …”

Section: Asymmetric Division To Balance Self-renewal and Differentiationmentioning

confidence: 99%

Germline stem cells: stems of the next generation

Yuan

Yamashita

2010

Current Opinion in Cell Biology

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Germline stem cells (GSCs) sustain gametogenesis during the life of organisms. Recent progress has substantially extended our understanding of GSC behavior, including the mechanisms of stem cell self-renewal, asymmetric stem cell division, stem cell niches, dedifferentiation, and tissue aging. GSCs typically are highly proliferative, due to organismal requirement to produce large number of differentiated cells. While many somatic stem cells are multipotent, with potentially multiple differentiation pathways, GSCs are unipotent. For these relatively simple characteristics (e.g. constant proliferation and unipotency), GSCs have served as ideal model systems for the study of adult stem cell behavior, leading to many important discoveries. Here, we summarize recent progress in GSC biology, with an emphasis on evolutionarily conserved mechanisms.

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Interpreting spatial information and regulating mitosis in response to spindle orientation: Figure 1.

Cited by 8 publications

References 42 publications

Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit

Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit

Regulation of cyclin A localization downstream of Par-1 function is critical for the centrosome orientation checkpoint in Drosophila male germline stem cells

Germline stem cells: stems of the next generation

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