--- module: 082-03 language: en chapter: 82 title: "Cell Architecture, Organelles, Cytoskeleton, Trafficking, and the Cell Cycle" module_title: "Cell-cycle control, division, stem cells, senescence, and experimental observation" source_sha256: db62547f79ab9418d2c2e3c6490e33385c272b1f925bec9840c59970b3912f33 --- # Cell cycle, stem cells, senescence, and methods ## Cycle phases and fates ### Gap one, synthesis, gap two, mitosis ### G zero quiescence is reversible ### Other exits: differentiation, senescence, death ### Tissues balance outcomes by signals and context ## Cyclin-dependent kinase control ### Stage-specific cyclins activate kinases #### Cyclin D with four or six: mitogens #### Cyclin E with two: synthesis entry #### Cyclin B with one: mitosis ### Ubiquitin destruction makes transitions one-way ### Restriction point commits to division #### Phosphorylated retinoblastoma protein frees E two F #### Loss of control drives proliferation ### Growth signals and nutrients gate division #### Rapamycin target integrates nutrients and energy #### AMP-activated kinase suppresses anabolism ## Replication and checkpoints ### Origins licensed before synthesis #### Activation blocks relicensing ### Replication stress from stalled forks ### Ataxia telangiectasia mutated kinase #### Responds to double-strand breaks ### Related kinase: replication stress ### p fifty-three: p twenty-one arrest or apoptosis ### Gap two switch into mitosis #### Phosphatases remove inhibitory phosphate #### Positive feedback prevents mixed states ## Mitosis and cytokinesis ### Cohesin holds sister chromatids ### Kinetochores attach to spindle microtubules #### Bi-orientation creates tension #### Attachment matters more than alignment ### Spindle-assembly checkpoint blocks anaphase #### Anaphase-promoting complex targets securin #### Separase cleaves cohesin ### Contractile ring and abscission ### Errors: tetraploidy, micronuclei, aneuploidy ## Meiosis ### One replication, two divisions ### Homologues recombine in first prophase #### Recombination aids correct segregation ### Meiosis one separates homologues ### Meiosis two separates sisters ### Maternal arrest raises aneuploidy with age ## Quiescence and stem cells ### Quiescence is active and often reversible ### Neurons and cardiomyocytes rarely cycle ### Symmetric divisions expand or deplete pool ### Asymmetric outcome keeps one stem-like daughter ### Transit-amplifying cells divide briefly ### Potency: totipotent, pluripotent, multipotent #### Induced pluripotent cells model disease ### Niche signals maintain stem-cell behaviour ## Senescence, telomeres, and cell death ### Senescence is durable proliferation arrest #### Secretory phenotype: cytokines, proteases #### Acute helps, chronic drives inflammation ### Short telomeres trigger damage response #### Not a simple biological clock ### Apoptosis without immediate membrane rupture #### Intrinsic: cytochrome c activates caspases #### Extrinsic: death receptors ### Regulated necrosis: necroptosis, pyroptosis, ferroptosis ## Observing cells ### Bright-field, phase-contrast, fluorescence ### Confocal sectioning and super-resolution ### Electron microscopy needs fixed specimens ### Colocalisation does not prove interaction ### Controls: positive, negative, no primary antibody ### Flow cytometry measures DNA content #### Gap two and mitosis not separated #### Histone H three phosphorylation marks mitosis ## Models and perturbation ### Primary cells short-lived, lines may be misidentified ### Plastic imposes unnatural stiffness ### Organoids and chips remain incomplete ### Loss- and gain-of-function tools #### Off-target effects and compensation #### Rescue strengthens causal inference ### Single-cell analysis reveals heterogeneity