Origin of cell division as one of the deepest mysteries

Tissue stem cells (TSCs) exist in most embryonic and adult organs, have self-renewal potential, and the ability to differentiate more than one cell type in specific tissues. During development, TSCs give rise to several cell lineages to construct and form organs. [...] it is still unknown what physiological compounds could fragment mitochondria in TM cells by antigen stimulation [...] [...] it is fascinating for future studies how mitochondrial dynamics is involved in this lineage reprogramming process beyond as a metabolic controller, probably coordinating with signalling cascades.

Mitochondrial dynamics coordinate cell differentiation Masafumi Noguchi, Atsuko Kasahara DOI: 10.1016/j.bbrc.2017.06.094 Biochemical and Biophysical Research Communications

Complex, functionally specified informational complexity. Dionisio

[...] miR-7 acts to buffer the development of both the medulla and the eye, two tissues that will directly communicate in the adult brain. The presence of miR-7 in both the eye imaginal disc and the optic lobe represents an independent but conserved buffer that operates to coordinate appropriate developmental progression in each system, in spite of external environmental fluctuations. The presence of this common buffer provides robustness within each system that may contribute to ensuring the eventual connectivity required for retinotopic mapping of the visual system.

miR-7 Buffers Differentiation in the Developing Drosophila Visual System Elizabeth E. Caygill and Andrea H. Brand DOI: 10.1016/j.celrep.2017.07.047 Cell Reports 20, 1255–1261

Complex, functionally specified informational complexity. Dionisio

Drosophila vision requires the accurate specification of over 80 different types of optic lobe neurons and the establishment of precise visual circuits between the neurons of the optic lobe and the photoreceptors of the eye. [...] the role of miR-7 is to act as a buffer to ensure the timely and precise transition from neuroepithelial cells to neuroblasts in the developing optic lobe.

miR-7 Buffers Differentiation in the Developing Drosophila Visual System Elizabeth E. Caygill and Andrea H. Brand DOI: 10.1016/j.celrep.2017.07.047 Cell Reports 20, 1255–1261

Complex, functionally specified informational complexity. Dionisio

[...] microRNA miR-7 is expressed at the transition between neuroepithelial cells and neuroblasts. [...] miR-7 promotes neuroepithelial cell-to-neuroblast transition by targeting downstream Notch effectors to limit Notch signaling. miR-7 acts as a buffer to ensure that a precise and stereotypical pattern of transition is maintained, even under conditions of environmental stress, echoing the role that miR-7 plays in the eye imaginal disc. This common mechanism reflects the importance of robust visual system development.

miR-7 Buffers Differentiation in the Developing Drosophila Visual System Elizabeth E. Caygill and Andrea H. Brand DOI: 10.1016/j.celrep.2017.07.047 Cell Reports 20, 1255–1261

Complex, functionally specified informational complexity. Dionisio

The switch from neuroepithelial cells to neuroblasts is controlled by a complex gene regulatory network and is marked by the expression of the proneural gene l’sc.

miR-7 Buffers Differentiation in the Developing Drosophila Visual System Elizabeth E. Caygill and Andrea H. Brand DOI: 10.1016/j.celrep.2017.07.047 Cell Reports 20, 1255–1261

Complex, functionally specified informational complexity. Dionisio

Although we cannot explain why underrotated ommatidial clusters were mainly observed in such discs, incorrect R3/R4 cell fate specification could affect the degree/direction of ommatidial rotation. Microtubules are an important component of the cytoskeleton and are dynamically assembled from a- and b-tubulin heterodimers. Tubulins are encoded in multiple gene families, each member of which is expressed in a specific tissue and temporal pattern. [...] trafficking of Sca vesicles depends on dynein/kinesin function [...]

Scabrous Overexpression in the Eye Affects R3/R4 Cell Fate Specification and Inhibits Notch Signaling Veronica Munoz-Soriano, Diego Santos, Fabrice C. Durupt, Sandra Casani and Nuria Paricio DEVELOPMENTAL DYNAMICS 245:166–174 DOI: 10.1002/DVDY.24362

Complex, functionally specified informational complexity. Dionisio

Epithelial planar cell polarity (PCP) in the Drosophila eye is reflected by the regular arrangement of 800 visual units called ommatidia. Unexpectedly, we found that sev>sca eyes mainly contained ommatidia with chirality defects (54.4%64.0) reflected by a high percentage of symmetrical (or achiral) ommatidia and some chirality flips [...]

Scabrous Overexpression in the Eye Affects R3/R4 Cell Fate Specification and Inhibits Notch Signaling Veronica Munoz-Soriano, Diego Santos, Fabrice C. Durupt, Sandra Casani and Nuria Paricio DEVELOPMENTAL DYNAMICS 245:166–174 DOI: 10.1002/DVDY.24362

Did somebody say "Unexpectedly"? Complex, functionally specified informational complexity. Dionisio

[...] sca overexpression antagonizes Notch signaling in the Drosophila eye, and are inconsistent with Sca being an ommatidial rotation-specific factor. [...] microtubule motors and other proteins involved in intracellular transport are related with Sca function.

Scabrous Overexpression in the Eye Affects R3/R4 Cell Fate Specification and Inhibits Notch Signaling Veronica Munoz-Soriano, Diego Santos, Fabrice C. Durupt, Sandra Casani and Nuria Paricio DEVELOPMENTAL DYNAMICS 245:166–174 DOI: 10.1002/DVDY.24362

Complex, functionally specified informational complexity. Dionisio

Future work involving the connection between the microtubule network and the ER may help shed light on the role of Jagn in mitotic spindle positioning. [...] the ER may be playing a greater role in development and cell fate selection. The mechanism that governs asymmetric division consist of two events: establishment of cell polarity, and a mechanism of spindle alignment along this polarity axis [...] Future studies investigating the coordination of mitotic spindle events and ER movement through these divisions during development will further elucidate the molecular mechanisms required for asymmetric organelle division and generation of cellular diversity.

The Endoplasmic Reticulum is partitioned asymmetrically during mitosis prior to cell fate selection in proneuronal cells in the early Drosophila embryo Anthony S. Eritano, Arturo Altamirano, Sarah Beyeler, Norma Gaytan, Mark Velasquez, and Blake Riggs doi: 10.1091/mbc.E16-09-0690 Mol. Biol. Cell mbc.E16-09-0690

Complex, functionally specified informational complexity. Dionisio

A fundamental step in the development of a multicellular organism is the generation of cellular diversity. The correct establishment of cell polarity has been demonstrated to be critical for cell fate selection [...] Establishment of cell polarity relies on the correct positioning of cell fate determinants [...] [...] changes in cellular organization prior to an asymmetric division are poorly understood and the cue preceding these divisions and the subsequent establishment of cell fate has yet to be identified.

The Endoplasmic Reticulum is partitioned asymmetrically during mitosis prior to cell fate selection in proneuronal cells in the early Drosophila embryo Anthony S. Eritano, Arturo Altamirano, Sarah Beyeler, Norma Gaytan, Mark Velasquez, and Blake Riggs doi: 10.1091/mbc.E16-09-0690 Mol. Biol. Cell mbc.E16-09-0690

Complex, functionally specified informational complexity. Dionisio

Asymmetric cell division is the primary mechanism to generate cellular diversity and relies on the correct partitioning of cell fate determinants. However, the mechanism by which these determinants are delivered and positioned is poorly understood and the upstream signal to initiate asymmetric cell division is currently unknown. The results presented here describe a striking model in which an organelle is partitioned asymmetrically in an otherwise symmetrically dividing cell population just upstream of cell fate determination, and updates previous models of spindle-based selection of cell fate during mitosis.

The Endoplasmic Reticulum is partitioned asymmetrically during mitosis prior to cell fate selection in proneuronal cells in the early Drosophila embryo Anthony S. Eritano, Arturo Altamirano, Sarah Beyeler, Norma Gaytan, Mark Velasquez, and Blake Riggs doi: 10.1091/mbc.E16-09-0690 Mol. Biol. Cell mbc.E16-09-0690

Complex, functionally specified informational complexity. Dionisio

Stem Cell Orchestra https://stemcellorchestra.wordpress.com/

Complex, functionally specified informational complexity. Dionisio

These findings reveal a previously unknown effect of BRCA1 suppression on mechanisms that regulate the cell division axis in proliferating, non-transformed human mammary epithelial cells and consequent downstream effects on the mitotic integrity and phenotype control of their progeny.

BRCA1 controls the cell division axis and governs ploidy and phenotype in human mammary cells. He Z1, Kannan N2,3, Nemirovsky O1, Chen H1, Connell M1, Taylor B4, Jiang J1, Pilarski LM4, Fleisch MC5, Niederacher D6, Pujana MA7, Eaves CJ2,8, Maxwell CA1 Oncotarget. 2017 May 16;8(20):32461-32475. doi: 10.18632/oncotarget.15688.

Complex, functionally specified informational complexity. :) Dionisio

Interesting questions are therefore raised about the similarities and differences between the G1 and G2 checkpoints and their implications for the effect of G2 checkpoint interference on the G1 checkpoint. [...] the G2 checkpoint is an ingenious node?based molecular switch which outcome is determined by the interplay of the PLK1, CHK1, Wee1, CDC25C and CDK1 nodes that are influenced by DNA damage and repair signaling. Together, this system allows the cell to intricately relay DNA status information to the cell cycle machinery, making it a pivotal process in maintaining cellular integrity.

The G2 checkpoint—a node?based molecular switch Mark C. de Gooijer, 1 Arnout van den Top, 1 Irena Bockaj, 1 Jos H. Beijnen, 2 , 3 , 4 Thomas Würdinger, 5 , 6 , 7 and Olaf van Tellingen FEBS Open Bio. 2017 Apr; 7(4): 439–455. doi: 10.1002/2211-5463.12206

Complex complexity Dionisio

The G1 and G2 checkpoints, although differing in the involvement of specific checkpoint proteins, are in essence node?based systems revolving around a pivotal CDK node that controls cell cycle progression [...] Although the last two decades have generated a framework of the biomolecular network of the G2 checkpoint, many interesting questions remain. Several steps of the G2 network remain to be elucidated in full detail [...]

The G2 checkpoint—a node?based molecular switch Mark C. de Gooijer, 1 Arnout van den Top, 1 Irena Bockaj, 1 Jos H. Beijnen, 2 , 3 , 4 Thomas Würdinger, 5 , 6 , 7 and Olaf van Tellingen FEBS Open Bio. 2017 Apr; 7(4): 439–455. doi: 10.1002/2211-5463.12206

Complex complexity Dionisio

Tight regulation of the eukaryotic cell cycle is paramount to ensure genomic integrity throughout life. Cell cycle checkpoints are present in each phase of the cell cycle and prevent cell cycle progression when genomic integrity is compromised. The G2 checkpoint is an intricate signaling network that regulates the progression of G2 to mitosis (M).

The G2 checkpoint—a node?based molecular switch Mark C. de Gooijer, 1 Arnout van den Top, 1 Irena Bockaj, 1 Jos H. Beijnen, 2 , 3 , 4 Thomas Würdinger, 5 , 6 , 7 and Olaf van Tellingen FEBS Open Bio. 2017 Apr; 7(4): 439–455. doi: 10.1002/2211-5463.12206

Complex complexity Dionisio

[...] it is paramount to keep MASTL inactive during the G2 DNA damage checkpoint. [...] it is intriguing that the level of MASTL differs considerably between different cancer cell lines [...] It will be interesting to expand our limited understanding of whether MASTL plays a role in tumorigenesis.

MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation Po Yee Wong,1 Hoi Tang Ma,1 Hyun-jung Lee,1 and Randy Y. C. Poona Sci Rep. 2016; 6: 22230. doi: 10.1038/srep22230

Complex complexity Dionisio

[...] MASTL may be particularly important for cell cycle reentry after DNA damage, when all the cyclin B–CDK1 complexes are in the inhibitory state. Development of specific MASTL inhibitors should assist the study of this pathway in the future. [...] it is not immediately obvious how a phosphatase pathway could regulate both APC/CCDC20 and APC/CCDH1 equally.

MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation Po Yee Wong,1 Hoi Tang Ma,1 Hyun-jung Lee,1 and Randy Y. C. Poona Sci Rep. 2016; 6: 22230. doi: 10.1038/srep22230

Complex complexity Dionisio

Greatwall kinase (MASTL in human) has emerged as a key player for mitosis. Greatwall/MASTL plays a pivotal role in maintaining CDK1-dependent phosphorylation during mitosis CDK1 activates Greatwall/MASTL during mitosis in a positive feedback loop

MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation Po Yee Wong,1 Hoi Tang Ma,1 Hyun-jung Lee,1 and Randy Y. C. Poona Sci Rep. 2016; 6: 22230. doi: 10.1038/srep22230

Complex complexity Dionisio

The G2 DNA damage checkpoint is one of the most important mechanisms controlling G2–mitosis transition. The kinase Greatwall (MASTL in human) promotes normal G2–mitosis transition by inhibiting PP2A via ARPP19 and ENSA. [...] precise control of MASTL is essential to couple DNA damage to mitosis through the rate of mitotic entry and APC/C activation.

MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation Po Yee Wong,1 Hoi Tang Ma,1 Hyun-jung Lee,1 and Randy Y. C. Poona Sci Rep. 2016; 6: 22230. doi: 10.1038/srep22230

Complex complexity Dionisio

The cell division ballet --specially the asymmetric mitosis-- along with gastrulation, morphogenesis, organogenesis, and other developmental processes, make the bacteria flagellum look like a Lego for toddlers. The whole biology is filled with amazing things. It's obvious we're seeing the most fascinating complex functional specified information-processing system ever imagined. Even the ongoing reductionist bottom-up reverse-engineering research is making "surprising" and "unexpected" discoveries that shed light on the elaborate cellular and molecular choreographies orchestrated within the wonderfully designed biological systems. We ain't seen nothin' yet. The most fascinating discoveries are still ahead. Let's fasten our seatbelts. This ride is just starting. True Wonder Beyond Glorieta... (c) Unending Revelation of the Ultimate Reality. (c) Dionisio

[...] MASTL might safeguard DNA integrity during mitosis in rapidly dividing mouse PGCs. PGCs are specified after receiving bone morphogenetic protein (BMP) signals from the extraembryonic tissues and they are among the first lineages to be established in embryos [...] [...] there are only a limited number of studies on the mechanisms underlying the proliferation of PGCs. We believe that our findings are valuable for studying cell cycle regulation in PGCs in the context of the reported mechanisms of PGC proliferation. [...] Mastl is an indispensable gene involved in the mitotic progression in PGCs, which prevents mitotic catastrophe and the apoptotic cell death of PGCs. [...] this study expands our understanding of how the cell cycle is regulated during the rapid proliferation of PGCs in developing embryonic gonad.

MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice Sanjiv Risal,1,6,* Jingjing Zhang,1,6 Deepak Adhikari,2 Xiaoman Liu,3 Jingchen Shao,1 Mengwen Hu,1 Kiran Busayavalasa,1 Zhaowei Tu,1 Zijiang Chen,3 Philipp Kaldis,4,5,* and Kui Liu Cell Discov. 2017; 3: 16052. Published online 2017 Feb 7. doi: 10.1038/celldisc.2016.52

Did somebody say "believe"? :) Complex complexity Dionisio

Primordial germ cells (PGCs) are embryonic cells that serve as progenitors of female and male gametes, and eventually differentiate into oocyte and sperm [...] [...] the molecular mechanisms regulating the cell cycle of proliferating PGCs between 9.5–12.5?dpc have not been investigated. The mammalian cell cycle is driven by sequential activation of different types of cyclin-dependent kinases [...] [...] phosphatase regulatory unit MASTL-PP2A has a fundamental role in mediating mouse PGC proliferation.

MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice Sanjiv Risal,1,6,* Jingjing Zhang,1,6 Deepak Adhikari,2 Xiaoman Liu,3 Jingchen Shao,1 Mengwen Hu,1 Kiran Busayavalasa,1 Zhaowei Tu,1 Zijiang Chen,3 Philipp Kaldis,4,5,* and Kui Liu Cell Discov. 2017; 3: 16052. Published online 2017 Feb 7. doi: 10.1038/celldisc.2016.52

Complex complexity Dionisio

In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. [...] MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis.

MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice Sanjiv Risal,1,6,* Jingjing Zhang,1,6 Deepak Adhikari,2 Xiaoman Liu,3 Jingchen Shao,1 Mengwen Hu,1 Kiran Busayavalasa,1 Zhaowei Tu,1 Zijiang Chen,3 Philipp Kaldis,4,5,* and Kui Liu1,3 Cell Discov. 2017; 3: 16052. doi: 10.1038/celldisc.2016.52

Complex complexity Dionisio

Kinetochores are macromolecular assemblies that connect chromosomes to spindle microtubules (MTs) during mitosis. The metazoan-specific ?800-kD ROD-Zwilch-ZW10 (RZZ) complex builds a fibrous corona that assembles on mitotic kinetochores before MT attachment to promote chromosome alignment and robust spindle assembly checkpoint signaling. Spindly, a dynein adaptor, is related to BicD2 and binds RZZ directly in a farnesylation-dependent but membrane-independent manner.

Structure of the RZZ complex and molecular basis of its interaction with Spindly. Mosalaganti S1, Keller J2, Altenfeld A2, Winzker M3, Rombaut P4, Saur M1, Petrovic A2, Wehenkel A2, Wohlgemuth S2, Müller F2, Maffini S2, Bange T2, Herzog F4, Waldmann H3,5, Raunser S6, Musacchio A7 J Cell Biol. 2017 Apr 3;216(4):961-981. doi: 10.1083/jcb.201611060

Complex complexity Dionisio

[...] the presence of dynein at kinetochores is required to turn off RZZ-mediated inhibition of NDC-80, but the mechanism remains unclear. An important unresolved question is whether functionally diverse dynein adaptors use similar mechanisms to interact with dynein and dynactin. It is likely that the importance of the pointed-end complex for dynactin function has so far been underestimated, [...] Further molecular and functional characterization of the interactions between dynein adaptors and the dynactin pointed-end promises to advance our understanding of how dynein is recruited and activated in different cellular contexts.

Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly. Gama JB, Pereira C, Simões PA, Celestino R, Reis RM, Barbosa DJ, Pires HR, Carvalho C, Amorim J, Carvalho AX, Cheerambathur DK, Gassmann R J Cell Biol. 2017 Apr 3;216(4):943-960. doi: 10.1083/jcb.201610108.

Complex complexity Dionisio

The molecular motor dynein is used in virtually all cellular processes that require microtubule minus end directed motility. Dynein’s functional diversity requires that the motor associate with cofactors and cargo-specific adaptors, but how dynein is recruited and locally activated at subcellular structures remains poorly understood.

Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly. Gama JB, Pereira C, Simões PA, Celestino R, Reis RM, Barbosa DJ, Pires HR, Carvalho C, Amorim J, Carvalho AX, Cheerambathur DK, Gassmann R J Cell Biol. 2017 Apr 3;216(4):943-960. doi: 10.1083/jcb.201610108.

Complex complexity Dionisio

Chromosome segregation during cell division requires attachments between spindle microtubules and kinetochores, multiprotein complexes that assemble on each sister chromatid. The microtubule-based motor cytoplasmic dynein 1 (dynein) localizes to the outermost layer of the kinetochore [...] [...] the mechanism used by Spindly to engage dynein and dynactin is also relevant for how the motor interacts with cargo adaptors in the context of intracellular transport.

Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly. Gama JB, Pereira C, Simões PA, Celestino R, Reis RM, Barbosa DJ, Pires HR, Carvalho C, Amorim J, Carvalho AX, Cheerambathur DK, Gassmann R J Cell Biol. 2017 Apr 3;216(4):943-960. doi: 10.1083/jcb.201610108.

Complex complexity Dionisio

The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. Conservation of Spindly-like motifs in adaptors involved in intracellular transport suggests a common mechanism for linking dynein to cargo.

Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly. Gama JB, Pereira C, Simões PA, Celestino R, Reis RM, Barbosa DJ, Pires HR, Carvalho C, Amorim J, Carvalho AX, Cheerambathur DK, Gassmann R J Cell Biol. 2017 Apr 3;216(4):943-960. doi: 10.1083/jcb.201610108.

Complex complexity Dionisio

Dynein removes the checkpoint proteins from kinetochores once chromosomes are bioriented. In this issue, Gama et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610108) and Mosalaganti et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611060) reveal the molecular basis for how dynein and its adaptor protein Spindly are recruited to the ROD-Zw10-Zwilch complex in the fibrous corona of unattached kinetochores.

Dynein at kinetochores: Making the connection. McHugh T, Welburn JP J Cell Biol. 2017 Apr 3;216(4):855-857. doi: 10.1083/jcb.201703054.

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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.

Complex complexity Dionisio

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

Complex complexity Dionisio

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

Complex complexity Dionisio

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 complexity Dionisio

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.

Complex complexity Dionisio

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.

Complex complexity Dionisio

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.pdf J-Mac

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