Cell-cycle phospho-regulation of the kinetochore

Klemm, Cinzia; Thorpe, Peter H.; Ólafsson, Guðjón

doi:10.1007/s00294-020-01127-2

Cited by 13 publications

(16 citation statements)

References 210 publications

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“…Accordingly, eukaryotic cell cycle regulation integrates a huge multitude of internal and external signals to optimize survival. Failures in these processes reduce cell survival and, in higher metazoans, lead to cancer, and other diseases ( Moriel-Carretero et al, 2019 ; She et al, 2019 ; Klemm et al, 2020 ; Lai et al, 2020 ; Matellán and Monje-Casas, 2020 ; Niwa, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System

Delgado-Román

Muñoz-Centeno

2021

Front. Mol. Biosci.

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Eukaryotic life is possible due to the multitude of complex and precise phenomena that take place in the cell. Essential processes like gene transcription, mRNA translation, cell growth, and proliferation, or membrane traffic, among many others, are strictly regulated to ensure functional success. Such systems or vital processes do not work and adjusts independently of each other. It is required to ensure coordination among them which requires communication, or crosstalk, between their different elements through the establishment of complex regulatory networks. Distortion of this coordination affects, not only the specific processes involved, but also the whole cell fate. However, the connection between some systems and cell fate, is not yet very well understood and opens lots of interesting questions. In this review, we focus on the coordination between the function of the three nuclear RNA polymerases and cell cycle progression. Although we mainly focus on the model organism Saccharomyces cerevisiae, different aspects and similarities in higher eukaryotes are also addressed. We will first focus on how the different phases of the cell cycle affect the RNA polymerases activity and then how RNA polymerases status impacts on cell cycle. A good example of how RNA polymerases functions impact on cell cycle is the ribosome biogenesis process, which needs the coordinated and balanced production of mRNAs and rRNAs synthesized by the three eukaryotic RNA polymerases. Distortions of this balance generates ribosome biogenesis alterations that can impact cell cycle progression. We also pay attention to those cases where specific cell cycle defects generate in response to repressed synthesis of ribosomal proteins or RNA polymerases assembly defects.

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Section: Introductionmentioning

confidence: 99%

Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System

Delgado-Román

Muñoz-Centeno

2021

Front. Mol. Biosci.

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“…Pools of evolutionarily conserved phosphatases are delivered to the kinetochore 32 , 33 by proteins capable of interacting with microtubules and essential for normal chromosome-microtubule attachment: CENP-E 34 , Astrin-SKAP/Kinastrin complex (referred as Astrin-SKAP here) 27 , 35 , SKA complex 36 and KNL1/hSPC105/Blinkin (referred as KNL1 here) 37 – 39 . While KNL1/hSPC105/Blinkin is a constitutive kinetochore protein 37 , 38 , CENP-E is localised to kinetochores during prometaphase and metaphase but not anaphase 40 .…”

Section: Introductionmentioning

confidence: 99%

Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation

et al. 2021

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Defects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome missegregation. Kinetochore-microtubule attachments that lack the opposing-pull are detached by Aurora-B/Ipl1. It is unclear how mono-oriented attachments that precede biorientation are spared despite the lack of opposing-pull. Using an RNAi-screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide evidence of domains in the microtubule-end associated protein that sense changes specific to end-on kinetochore-microtubule attachments and assemble an outer-kinetochore crescent to stabilise attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to preserve mono-oriented attachments. Thus, CIN prevention pathways are not only surveying attachment defects but also actively recognising and stabilising mature attachments independent of biorientation.

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“…Biochemical association of DDK with Cse4 begins in S phase and persists through mitosis (Mishra et al, 2021), while Cdc5 associates with Cse4 in G2/M phase (Mishra et al, 2016;Mishra et al, 2019). It is not known exactly when Cdc5 phosphorylates its many kinetochore substrates (Klemm et al, 2020;Lera et al, 2016;Olafsson and Thorpe, 2020). We favor a model in which DDK phosphorylates Mif2 at the G1/S transition, and this primes Mif2 for subsequent phosphorylation by Cdc5.…”

Section: Discussionmentioning

confidence: 91%

Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly

Hinshaw

Quan

Cai

et al. 2021

Preprint

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Kinetochores control eukaryotic chromosome segregation by connecting chromosomal centromeres to spindle microtubules. Duplication of centromeric DNA necessitates kinetochore disassembly and subsequent reassembly on the nascent sisters. To search for a regulatory mechanism that controls the earliest steps of kinetochore assembly, we studied Mif2/CENP-C, an essential basal component. We found that Polo-like kinase (Cdc5) and Dbf4-dependent kinase (DDK) phosphorylate the conserved PEST region of Mif2/CENP-C and that this phosphorylation directs inner kinetochore assembly. Mif2 phosphorylation promotes kinetochore assembly in a reconstituted biochemical system, and it strengthens Mif2 localization at centromeres in cells. Disrupting one or more phosphorylation sites in the Mif2-PEST region progressively impairs cellular fitness and sensitizes cells to microtubule poisons. The most severe Mif2-PEST mutations are lethal in cells lacking otherwise non-essential Ctf19 complex factors. These data suggest that multi-site phosphorylation of Mif2/CENP-C is a robust switch that controls inner kinetochore assembly, ensuring accurate chromosome segregation.

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Cell-cycle phospho-regulation of the kinetochore

Cited by 13 publications

References 210 publications

Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System

Coupling Between Cell Cycle Progression and the Nuclear RNA Polymerases System

Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation

Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly

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