Origin of cell division as one of the deepest mysteries

_{Denyse O'Leary

July 8, 2017

Cell biology, Intelligent Design, Origin Of Life}

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The origin of life is among the deepest unexplained mysteries. How did the first self-replicating entities emerge, providing the material on which the selective mechanism of evolution could then operate? The most primitive known self-replicating forms of life are far too complex to have sprung from the pre-evolutionary environment through… More.

You’d have to pay to read more. Not recommended. If they had any workable naturalist idea, the world would deafen at the sound. If they thought it required intelligence, their careers would be ruined.

See also: What we know and don’t know about the origin of life

Comments

Future studies will likely uncover additional mechanisms how SAC signalling is regulated in detail and new substrates of the Greatwall kinase/Mastl->PP2A/B55 pathway.
Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint. Diril MK1, Bisteau X1, Kitagawa M2, Caldez MJ1,3, Wee S1, Gunaratne J1,4, Lee SH2, Kaldis P1 PLoS Genet. 2016 Sep 15;12(9):e1006310. doi: 10.1371/journal.pgen.1006310

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The activity of Cdk1/cyclin B is essential for cells to enter and complete mitosis. [...] identifying specific targets of the Greatwall kinase/Mastl->PP2A/B55 pathway is essential for understanding its in vivo functions. Identifying the Cdk1-phosphorylated targets that need to be dephosphorylated to silence SAC is a major challenge [...]
Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint. Diril MK1, Bisteau X1, Kitagawa M2, Caldez MJ1,3, Wee S1, Gunaratne J1,4, Lee SH2, Kaldis P1 PLoS Genet. 2016 Sep 15;12(9):e1006310. doi: 10.1371/journal.pgen.1006310

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The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. [...] the molecular mechansims by which Mastl promotes proper chromosome segregation and mitotic progression remain elusive. [...] Mastl is required for multi-site phosphorylation of the essntial SAC protein MPS1 as well as robust MPS1 kinase activity in mitosis by inhibiting PP2A/B55-mediated MPS1 dephosphorylation.
Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint. Diril MK1, Bisteau X1, Kitagawa M2, Caldez MJ1,3, Wee S1, Gunaratne J1,4, Lee SH2, Kaldis P1 PLoS Genet. 2016 Sep 15;12(9):e1006310. doi: 10.1371/journal.pgen.1006310

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A further possible contribution to the destabilization of arrest could be that the intact septin hourglass inhibits Cdh1 at the bud neck. The mechanism by which this could be achieved remains to be determined; [...] [...] the transcriptional activity of the nucleolus as well as septin integrity regulate features of cell cycle arrest.
Nucleolar asymmetry and the importance of septin integrity upon cell cycle arrest Urvashi Rai, Fadi Najm, and Alan M. Tartakoff PLoS One. 2017; 12(3): e0174306. doi: 10.1371/journal.pone.0174306

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Orderly progression through the cell cycle depends on checkpoints that impose arrest if critical features of the cell are not prepared to advance. Without these surveillance mechanisms, catastrophic mistakes occur [...] [...] there is little information concerning the physical relation between the outer aspect of the NE and the cell cortex at this level.
Nucleolar asymmetry and the importance of septin integrity upon cell cycle arrest Urvashi Rai, Fadi Najm, and Alan M. Tartakoff PLoS One. 2017; 12(3): e0174306. doi: 10.1371/journal.pone.0174306

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Ji et al. speculate that Mps1 phosphorylates one substrate after the other in a “cascade”, though this remains to be tested. [...] this crucial part of the regulation is still only partly understood [...]
Micromanaging checkpoint proteins Andrea Ciliberto1 and Silke Hauf eLife. 2017; 6: e25001. doi: 10.7554/eLife.25001

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When cells divide, their chromosomes duplicate and a protein complex called the kinetochore assembles on each chromosome copy. Microtubules then attach to the kinetochores to pull the copies apart and segregate them between the newly forming cells. The mitotic checkpoint is a cellular safeguard that triggers the checkpoint signaling cascade if the microtubules do not attach properly to the kinetochores.
Micromanaging checkpoint proteins Andrea Ciliberto1 and Silke Hauf eLife. 2017; 6: e25001. doi: 10.7554/eLife.25001

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It is clear from this and previous studies that checkpoint signals can be initiated from several sites: kinetochores, nuclear pores, possibly spindle poles, a tetO array, and soluble hetero-dimers of KNL1Spc7-Mps1Mph1 in the nucleoplasm. It will be very interesting to see whether similar ectopic platforms can arrest larger vertebrate cells and, if so, whether apoptosis is induced as this could have therapeutic implications.
Generation of a Spindle Checkpoint Arrest from Synthetic Signaling Assemblies. Yuan I, Leontiou I, Amin P, May KM, Soper Ní Chafraidh S, Zlámalová E, Hardwick KG Curr Biol. 2017 Jan 9;27(1):137-143. doi: 10.1016/j.cub.2016.11.014

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The spindle checkpoint acts as a mitotic surveillance system, monitoring interactions between kinetochores and spindle microtubules and ensuring high-fidelity chromosome segregation [...] [...] spindle checkpoint arrest can be independent of their kinetochore, spindle pole, and nuclear envelope localization.
Generation of a Spindle Checkpoint Arrest from Synthetic Signaling Assemblies. Yuan I1, Leontiou I1, Amin P1, May KM1, Soper Ní Chafraidh S1, Zlámalová E1, Hardwick KG Curr Biol. 2017 Jan 9;27(1):137-143. doi: 10.1016/j.cub.2016.11.014.

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Accurate chromosome inheritance during cell division is necessary for the development and maintenance of all organisms. It is unclear how this signal could become diluted if it was restricted to the spindle compartment. Our studies offer clarification as to how dilution of “wait anaphase” signals could occur.
"Wait anaphase" signals are not confined to the mitotic spindle. Heasley LR1, Markus SM1, DeLuca JG Mol Biol Cell. 2017 May 1;28(9):1186-1194. doi: 10.1091/mbc.E17-01-0036

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The spindle assembly checkpoint ensures the faithful inheritance of chromosomes by arresting mitotic progression in the presence of kinetochores that are not attached to spindle microtubules. [...] anaphase inhibitors are diffusible and active outside the confines of the mitotic spindle from which they are derived.
"Wait anaphase" signals are not confined to the mitotic spindle. Heasley LR1, Markus SM1, DeLuca JG Mol Biol Cell. 2017 May 1;28(9):1186-1194. doi: 10.1091/mbc.E17-01-0036

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We have further demonstrated the importance of an Mps1-orchestrated phosphorylation cascade in forming and activating this catalytic platform. [...] the kinetochore targeting of Mps1 itself is directly controlled by kinetochore-microtubule attachment [...] [...] a unique signal-transducing principle of the spindle checkpoint that not only enables signal amplification but also keeps the final signaling output responsive to kinetochore attachment status.
A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling. Ji Z1, Gao H1, Jia L1, Li B1, Yu H1 Elife. 2017 Jan 10;6. pii: e22513. doi: 10.7554/eLife.22513.

Did somebody say "orchestrated"? Complex complexityDionisio_{July 10, 2017
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Faithful chromosome segregation is ensured by a cellular surveillance system termed the spindle checkpoint [...] During mitosis, the spindle checkpoint senses kinetochores that are not attached or improperly attached to spindle microtubules and enhances the production of the mitotic checkpoint complex (MCC) [...]
A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling. Ji Z1, Gao H1, Jia L1, Li B1, Yu H1 Elife. 2017 Jan 10;6. pii: e22513. doi: 10.7554/eLife.22513.

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The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. [...] Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.
A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling. Ji Z1, Gao H1, Jia L1, Li B1, Yu H1 Elife. 2017 Jan 10;6. pii: e22513. doi: 10.7554/eLife.22513.

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Next they admit that the origin of the first replicating cell is also one of the deepest enduring mysteries. It’s not surprising that it is a mystery because things this complex just do not happen by chance. What about the mystery of quantum processes being at the core of life itself? "Thus there are many claims that quantum mechanics plays a key role in the origin and/or operation of biological organisms". http://www.ijabbr.com/article_7899_ae298d7aad75be8b019d9b5e649e69b7.pdf What about the mystery of cell division (mitosis) itself being controlled by quantum entanglement? I bet it can be explained by the "third way" evolutionary mechanism... "It is proposed here that normal mirror-like mitosis is organized by quantum coherence and quantum entanglement among microtubule-based centrioles and mitotic spindles which ensure precise, complementary duplication of daughter cell genomes and recognition of daughter cell boundaries. http://www.quantumconsciousness.org/sites/default/files/New%20Theory%20Origin%20of%20Cancer%20Quantum%20Coherent%20Entanglement.pdfJ-Mac_{July 9, 2017
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Well, it's refreshing to hear honest confessions from the evolutionists. Here they admit that OoL is one of the deepest unexplained mysteries - without which they can't even get evolutionary processes going. If nature could not produce life from totally natural processes, then the possibility of intelligence being involved in the actual evolution of organisms cannot be philosophically or scientifically ruled out. Next they admit that the origin of the first replicating cell is also one of the deepest enduring mysteries. It's not surprising that it is a mystery because things this complex just do not happen by chance.tjguy_{July 9, 2017
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