Cell division articles within Nature

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  • Letter |

    Mutations in the subunits of BAF chromatin-remodelling complexes are frequently found in human cancer; here deletion of BAF subunits or expression of mutants of the ATPase subunit BRG1 attenuates genome-wide binding of topoisomerase IIα, resulting in tangled chromosomes, anaphase bridges and G2/M arrest.

    • Emily C. Dykhuizen
    • , Diana C. Hargreaves
    •  & Gerald R. Crabtree

  • Letter |

    Using a CO-FISH method with single-chromosome resolution, sister chromatids of the sex chromosomes, but not autosomes, are shown to segregate nonrandomly during asymmetric cell divisions of Drosophila male germline stem cells; this suggests that it is unlikely that nonrandom sister chromatid segregation serves to protect the ‘immortal strand’ to avoid replication-induced mutations as proposed previously.

    • Swathi Yadlapalli
    •  & Yukiko M. Yamashita

  • Letter |

    The current model to explain accurate chromosome segregation after DNA replication holds that kinetochore–microtubule attachments exert tension across the centromere and are stabilized by spatial separation from inner centromere-localized Aurora B; here an alternative model is presented, wherein active Aurora B produced by clustering is sufficient to ensure biorientation through a mechanism that is intrinsic to the kinetochore.

    • Christopher S. Campbell
    •  & Arshad Desai

  • Letter |

    A mechanism to explain chromosomal instability (CIN) in colorectal cancer is demonstrated; three new CIN-suppressor genes (PIGN, MEX3C and ZNF516) encoded on chromosome 18q are identified, the loss of which leads to DNA replication stress, resulting in structural and numerical chromosome segregation errors, which are shown to be identical to phenotypes seen in CIN cells.

    • Rebecca A. Burrell
    • , Sarah E. McClelland
    •  & Charles Swanton

  • News & Views |

    Tet proteins regulate gene expression by removing methyl groups from DNA bases. This activity may be a facilitating step in turning on the cell-division pathway that produces sperm and egg cells. See Letter p.443

    • Sylvain Guibert
    •  & Michael Weber

  • Letter |

    Structural and functional analysis of the centralspindlin complex shows that it connects the mitotic spindle to the plasma membrane during cytokinesis through interactions of the C1 domain of centralspindlin’s MgcRacGAP subunit with phosphoinositide lipids.

    • Sergey Lekomtsev
    • , Kuan-Chung Su
    •  & Mark Petronczki

  • Article |

    Single-molecule and ensemble assays are used to show that large T antigen, the replicative DNA helicase of the simian virus 40 (SV40), unwinds DNA as a single hexamer by steric exclusion and is able to bypass covalent DNA–protein crosslinks.

    • Hasan Yardimci
    • , Xindan Wang
    •  & Johannes C. Walter

  • Letter |

    A loss-of-function approach in mice is used to show that the methylcytosine dioxygenase Tet1 has a role in regulating meiosis and meiotic gene activation in female germ cells; Tet1 deficiency does not greatly affect genome-wide demethylation but has a more specific effect on the expression of a subset of meiotic genes.

    • Shinpei Yamaguchi
    • , Kwonho Hong
    •  & Yi Zhang

  • News & Views |

    A genome-wide characterization of active translation of messenger RNA following inhibition of mTOR will transform our view of this signalling protein's regulatory role in cancer. See Article p.55 & Letter p.109

    • Antonio Gentilella
    •  & George Thomas

  • Article |

    The crystal structure of fission yeast mitotic checkpoint complex (MCC) reveals how MCC assembly is regulated and the molecular basis of anaphase-promoting complex (APC/C) inhibition by MCC.

    • William C. H. Chao
    • , Kiran Kulkarni
    •  & David Barford

  • News & Views |

    The orchestration of cell division requires a programme of events choreographed by protein modification. A study shows that the relative activity of a phosphatase enzyme towards its substrates imposes order during the final act of division.

    • Curt Wittenberg

  • News |

    A magnetosensing bacterium bends its internal magnet to weaken it before cell division.

    • Ewen Callaway

  • News & Views |

    During cell division, the DNA-associated CENP-A protein recruits the kinetochore protein complex to assemble on chromosomes. A region of just six amino-acid residues earmarks CENP-A for this purpose. See Letter p.354

    • Alison Pidoux
    •  & Robin Allshire

  • Article |

    This study focuses on developing mouse skin where mitotic basal progenitor cells switch from symmetric divisions to asymmetric division concomitant with stratification. Using a novel technical approach, the genetic pathway regulating spindle orientation is dissected, providing the first direct evidence that the proteins governing spindle orientation (LGN, NuMA and Dctn1) promote asymmetric cell divisions regulated by Notch signalling in mammalian cells in vivo.

    • Scott E. Williams
    • , Slobodan Beronja
    •  & Elaine Fuchs

  • Article |

    The APC/C is a large multiprotein complex that functions as an E3 ubiquitin ligase to regulate the cell cycle. Here, the entire APC/C complex is reconstituted, and in combination with structural studies a pseudo-atomic model for 70% of the complex is provided. These results contribute towards a molecular understanding of the roles of individual subunits in APC/C assembly and their interactions with co-activators, substrates and regulatory proteins.

    • Anne Schreiber
    • , Florian Stengel
    •  & David Barford

  • Article |

    To investigate the core engine of the eukaryotic mitotic cycle, a minimal control network has been generated in fission yeast that efficiently sustains cellular reproduction. Orderly progression through the major events of the cell cycle is driven by oscillation of an engineered minimal CDK module lacking much of the canonical regulation.

    • Damien Coudreuse
    •  & Paul Nurse

  • Letter |

    During periods of fasting the liver produces ketone bodies, which the peripheral tissues can use as a source of energy. Here it is shown that fasting inhibits multi-component mTOR complex 1 (mTORC1) in the liver. Inhibition of mTORC1 is required for activation of PPARα, a master regulator that switches on genes involved in ketogenesis. Livers from aged mice have increased mTORC1 signalling, reduced PPARα activity, and reduced ketone production. The observation that mTORC1 promotes an ageing phenotype in the liver fits well with the observation that inhibition of this pathway increases lifespan in several organisms.

    • Shomit Sengupta
    • , Timothy R. Peterson
    •  & David M. Sabatini

  • Article |

    Haematopoietic stem cells (HSCs) are very sensitive to energetic and oxidative stress, and modulation of the balance between their quiescence and proliferation is needed to respond to metabolic stress while preserving HSCs' long-term regenerative capacity. Here the tumour suppressor Lkb1 is shown to promote stem-cell maintenance and tissue regeneration by regulating energy metabolism and by preventing aneuploidy.

    • Daisuke Nakada
    • , Thomas L. Saunders
    •  & Sean J. Morrison

  • News & Views |

    Accurate cell division depends on proper attachment of chromosomes to the microtubule-based division apparatus. An impressive in vitro study shows how applied force plays a pivotal part in regulating such attachment. See Letter p.576

    • Yuta Shimamoto
    •  & Tarun M. Kapoor

  • Letter |

    The kinetochore is a large protein complex that assembles on centromeric DNA and captures microtubules to mediate chromosome separation. These authors report the first purification of functional kinetochores. They also show that kinetochore particles maintain load-bearing associations with assembling and disassembling ends of single microtubules and that tension increases the lifetimes of the attachments directly. These results provide evidence that tension selectively stabilises kinetochore–microtubule interactions.

    • Bungo Akiyoshi
    • , Krishna K. Sarangapani
    •  & Sue Biggins

  • News & Views |

    One might think that aneuploidy — having an abnormal number of chromosomes — would be harmful, and would reduce an organism's fitness. Not necessarily: it all depends on the type of aneuploidy and the associated conditions. See Letter p.321

    • Judith Berman

  • News & Views |

    Stem cells can renew themselves indefinitely — a feature that is often attributed to asymmetrical cell division. Fresh experimental and mathematical models of the intestine provide evidence that begs to differ.

    • Michael P. Verzi
    •  & Ramesh A. Shivdasani

  • Article |

    The Ndc80 complex is a key component of kinetochore that mediates direct interaction with spindle microtubules. These authors present a cryo-electron microscopy reconstruction of Ndc80 bound to microtubules. They find that Ndc80 uses a novel microtubule recognition mode coupling tubulin binding to self-oligomerization of the complex, and present a mechanistic model for the formation of high-affinity kinetochore–microtubule attachments during cell division.

    • Gregory M. Alushin
    • , Vincent H. Ramey
    •  & Eva Nogales

  • Letter |

    Cells that make up the liver are known to be polyploid. These authors show that mouse hepatocytes can increase and decrease their ploidy in vivo; increases occur as a result of failed cytokinesis, and decreases occur as a result of multipolar mitosis. The resulting genetic heterogeneity might be advantageous following hepatic injury, allowing the selection of 'genetically robust' cells from a pre-existing pool of diverse genotypes.

    • Andrew W. Duncan
    • , Matthew H. Taylor
    •  & Markus Grompe

  • Letter |

    Cell cycle checkpoints, such as the S-phase checkpoint, delay cell division to give the cell time to repair any damaged DNA. Here it is shown that the MLL gene — frequently disrupted in leukaemia — is part of the S-phase checkpoint. When DNA is damaged, MLL is phosphorylated by the ATR protein, causing MLL to accumulate on chromatin and methylate histone H3 on lysine 4. This delays DNA replication. MLL translocations, such as those that occur in leukaemia, disrupt this pathway and cause genomic instability.

    • Han Liu
    • , Shugaku Takeda
    •  & James J.-D. Hsieh

  • Letter |

    The mitotic spindle plays a key part in determining the site of the cleavage furrow in dividing metazoan cells. But are other mechanisms also involved? Here evidence is provided for a spindle-independent pathway for furrow positioning that occurs during asymmetric divisions of Drosophila neuroblast cells. The pathway involves the Pins protein complex, which polarizes furrow-forming proteins to the basal cortex of the cell. This mechanism might also occur in other highly polarized cell types.

    • Clemens Cabernard
    • , Kenneth E. Prehoda
    •  & Chris Q. Doe

  • News & Views |

    The retinoblastoma protein is essential for accurate DNA replication, and its loss is commonly associated with cancer. It emerges that this protein also regulates another stage of the cell cycle.

    • Giovanni Bosco

  • Letter |

    The chromosomal passenger complex (CPC) coordinates several processes during cell division, including chromosome bi-orientation and cytokinesis, and its proper localization is crucial. These authors provide a mechanism for its localization to the inner centromere. Cdk1–cyclin-B-dependent phosphorylation of the CPC promotes binding to shugoshin, which the authors define as a conserved centromeric adaptor of the CPC. This mechanism is conserved between fission yeast and human cells and highlights a crucial role of Cdk1–cyclin B in chromosome bi-orientation.

    • Tatsuya Tsukahara
    • , Yuji Tanno
    •  & Yoshinori Watanabe

  • Letter |

    These authors show that the JmjC domain-containing protein PHF8 has histone demethylase activity against H4K20me1 and is linked to two distinct events during cell cycle progression. PHF8 is recruited to the promoters of genes involved in the G1–S phase transition, where it removes H4K20me1 and contributes to gene activation, whereas dissociation of PHF8 from chromatin in prophase allows H4K20me1 to accumulate during mitosis.

    • Wen Liu
    • , Bogdan Tanasa
    •  & Michael G. Rosenfeld

  • Letter |

    Cyclin F is the founding member of the F-box protein family but its functions are unknown; unlike most cyclins, it does not bind or activate cyclin-dependent kinases. Here the authors identify CP110, a protein essential for centrosome duplication, as a substrate of Cyclin F. CP110 and Cyclin F associate on centrioles during the cell cycle, and Cyclin F is proposed to limit centrosome duplication by targeting CP110 for degradation.

    • Vincenzo D’Angiolella
    • , Valerio Donato
    •  & Michele Pagano

  • Article |

    Dynamin is a protein that catalyses the fission of clathrin-coated endocytic vesicles from cellular membranes. To carry out fission, it must hydrolyse GTP. The mechanism by which it does so is unknown, although it does require dynamin's GTPase effector domain (GED). Here, the structure of a minimal GTPase–GED fusion protein constructed from human dynamin 1 is presented. The structure reveals the catalytic machinery and provides new insight into the mechanisms underlying dynamin-catalysed membrane fission.

    • Joshua S. Chappie
    • , Sharmistha Acharya
    •  & Fred Dyda

  • Article |

    High-throughput microscopy combined with gene silencing by RNA interference is a powerful method for studying gene function. Here, a genome-wide method is presented for phenotypic screening of each of the ∼21,000 human protein-coding genes, using two-day imaging of dividing cells with fluorescently labelled chromosomes. The method enabled the identification of hundreds of genes involved in biological functions such as cell division, migration and survival.

    • Beate Neumann
    • , Thomas Walter
    •  & Jan Ellenberg

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