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Cover Image
Cover Image
On the cover
Cells replicate their genome in a well-defined order. The bottom three nuclei show active sites of DNA synthesis (red) at different stages of S phase. This program is set at the “timing decision point” (TDP) during G1. A post-TDP nucleus replicating in vitro (top right) follows the program, indicated by the colocalization (white) of DNA synthesis and late-replicating heterochromatin (blue), whereas a pre-TDP nucleus (top) shows no colocalization. Lu et al. reveal that the timing information is lost in G2 nuclei (top left).
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In This Issue
In Focus
In search of lost timing
Researchers learn more about how cells schedule DNA replication by determining when they tear up the timetable.
People & Ideas
Joan Brugge: Running rings around cancer
Brugge has devoted her career to uncovering how perturbations in normal cellular processes give rise to cancer.
Review
Report
Vertebrate kinetochore protein architecture: protein copy number
The stoichiometry of kinetochore components is determined, suggesting conservation between multiple microtubule-binding vertebrate and single microtubule-binding yeast kinetochores.
Tubulin polyglutamylation stimulates spastin-mediated microtubule severing
Microtubules with long polyglutamylated C-terminal tails are more prone to severing by spastin, establishing the importance of tubulin posttranslational modifications.
Role of kinase-independent and -dependent functions of FAK in endothelial cell survival and barrier function during embryonic development
Vascular development in mice only requires kinase-independent functions of FAK until E13.5, but kinase activity is needed for embryogenesis to complete.
Article
G2 phase chromatin lacks determinants of replication timing
Chromatin spatial organization helps establish the replication timing decision point at early G1. However, at G2, although retained, chromatin organization is no longer necessary or sufficient to maintain the replication timing program.
A robust cell cycle control mechanism limits E2F-induced proliferation of terminally differentiated cells in vivo
Overexpression of both CycE and E2F is necessary to trigger cell cycle reentry and overproliferation of terminally differentiated wing cells.
MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening
An RNAi screen determines that the early secretory pathway is subject to phosphoregulation via a variety of signaling pathways, including a link between growth factor signaling and ER export.
Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms
Kinesin-2 motor KIF17 autoinhibition is visualized in vivo; in the absence of cargo, this homodimer’s C-terminal tail blocks microtubule binding, and a coiled-coil segment blocks motility.
Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair
Lysosomal enzyme acid sphingomyelinase is released extracellularly when cells are wounded, converting sphingomyelin to ceramide and inducing endosome formation to internalize membrane lesions.
The small GTPases ARL-13 and ARL-3 coordinate intraflagellar transport and ciliogenesis
Cilia intraflagellar transport and ciliogenesis are regulated by two small GTPases that maintain binding between IFT subcomplexes.
