| Term | Definition |
|---|
| G1 interphase | growth in size without division, cell type+environ. = length of time |
| Myostatin | inhibits proliferation of myoblasts that fuse to form skeletal muscle |
| Myostatin blocks myoblasts at what transition | at G1 to S transition |
| Lack of myostatin in knockout mice and due to selective cattle breeding leads to | muscle proliferation |
| Human myostatin mutation | Splicing. heterozygous in Mom, homozygous in child. Child with massive muscle hypertrophy and musculature |
| Senescence- | a period where cells no longer divide |
| Fibroblast senescence correlates with | organism life span |
| Werner syndrome | premature aging disease, DNA helicase mutation, telomeres shorter, chromosome instability, fibroblasts have fewer divisions than normal before senescence |
| fibroblasts from heavy smokers have | decreased Werner syndrome protein |
| Mitotic apparatus components and function | spindle microtubules, centrosomes, kinetochores. drives the movement of chromosomes |
| Spindle microtubules | Replace interphase microtubules, Originate in pericentriolar material of centrosome, associated with molecular motors that drive movement on microtubules |
| Three types spindle microtubules | astral, kinetochore, overlap |
| Astral microtubules | orient contractile ring and spindle |
| Kinetochore microtubules | attach chromosomes to spindle, direct chromosome migration |
| Overlap microtubules | push spindle poles apart in anaphase (also called polar microtubules) |
| Centrosomes | Composed of centriole pair (short microtubules) and jelly-like pericentriolar material, Migrate to opposite ends of cell at beginning of mitosis, Also called spindle poles after migration |
| Kinetochores | attach spindle microtubules to the centromeres of each sister chromatid on the mitotic chromosomes, Needed for movement during prometaphase and anaphase, One kinetochore per chromatid |
| Prophase | Condensation of chromatin into "mitotic chromosome" |
| Condensins | complete the condensation of chromatin. Nuclear lamins+envelope breakdown, disperse in cytoplasm |
| Cohesins | "glue" together the sister chromatids at centromere and along the length of the mitotic chromosome |
| Each centromere is bound by a | kinetochore, which connects to spindle microtubules (2 kinetochores per mitotic chromosome, 1 per chromatid) |
| Disappearance of nuclear envelope defines | the end of prophase |
| M-Cdk | a complex of Cdk and mitotic cyclin |
| Activation of M-Cdk is required to | enter mitosis |
| Inactivation of M-Cdk is required to | leave mitosis |
| Mitotic cyclin (M-cyclin) levels and M-Cdk activity | cycle with the cell cycle, while Cdk protein levels do not cycle |
| Mitotic cyclin levels increase during | interphase, reach a threshold in G2 to activate M-Cdk |
| M-Cdk is inactivated by | proteolysis of mitotic cyclin by APC at metaphase-anaphase transition |
| Phosphorylation of Mcdk by a stimulatory kinase (CAK) | activates M-Cdk |
| Phosphorylation by an inhibitory kinase (Wee1) | inactivates M-Cdk |
| Inhibitory phosphorylation is dominant | over the stimulatory phosphorylation. Thus, M-Cdk is activated by a phosphatase that removes an inhibitory phosphate. This is the final step in activation of M-Cdk |
| Positive feedback activation of M-Cdk | M-Cdk activates the phosphatase cdc25 and inhibits the inhibitory kinase Wee1, which results in rapid activation of many M-Cdk molecules |
| Prometaphase | Alignment of all the chromosomes along midline of mitotic spindle |
| Metaphase | Period of inactivity while chromosomes are at the midzone, Check point for correct spindle attachments of chromosomes |
| In metaphase Mitosis is arrested since | the normal inactivation of M-Cdk is blocked by a signal from free kinetochores |
| Colchicine used to arrest cells for karyotyping | since it keeps kinetochores unattached |
| Metaphase to anaphase transition is initiated by | anaphase-promoting complex (APC) |
| APC is a highly regulated | ubiquitin ligase that tags proteins for proteolysis |
| APC is activated by | an activating subunit (Cdc20) and by phosphorylation by M-Cdk |
| APC is inhibited by | signal from free kinetechores |
| Activated APC triggers | M-cyclin proteolysis, which inactivates M-Cdk, allowing cell to leave mitosis |
| Anaphase | Triggered by inactivation of M-Cdk (degradation of cyclin) by APC APC control of chromatid links: APC initiates sister chromatid separation to allow movement to opposite spindle poles. APC cleaves an inhibitory subunit called securin. Securin normally keeps the protease separase inactive. Separase cleaves the cohesins, allowing chromatids to separate |
| APC cleaves an inhibitory subunit called | securin |
| Securin normally keeps | the protease separase inactive |
| Separase cleaves the | cohesins, allowing chromatids to separate |
| Transitions through the checkpoints are controlled by the activity of | cyclin dependent kinases (Cdks) that require binding of cyclin proteins |
| DNA damage checkpoint | p53 is required for detection of DNA damage (e.g. radiation therapy) |
| Ataxia telangiectasia | p53 not activated, so cells not arrested by DNA damage, Increased cancer incidence |
| Coordination of cellular events at each checkpoint by | the Cdks. |
| M-Cdk induces downstream events by | phosphorylation of specific proteins |
| Phos. Nuclear lamin filaments | causes dissociation of nuclear lamina |
| Phos. Histone H1, condensins | causes condensation of chromatin |
| Phos. Spindle microtubules | causes formation of mitotic apparatus |
| Phos. APC (may be indirect) | Is required for metaphase-anaphase transition and allows negative feedback regulation of M-Cdk |
| Phos. Cdc25 phosphatase | Is required for activation of M-Cdk and allows positive feedback regulation of M-Cdk |
| Separase activates a ___________ that dephosphorylates________ to make it more susceptible to __________: | phosphatase, securin, ubiquitination by APC |
| Separase activates a phosphatase that dephosphorylates: | securin to make it more susceptible to ubiquitination by APC |
| recall APC degrades securin to: | activate separase = positive feedback loop |
| Inhibitory phosphate is added at APC by | M-Cdk |
| APC activity drops after mitosis since: | M-Cdk is not active |
| APC tagged mitotic cyclin for: | degradation) = negative feedback loop |
| Telophase: | Reassembly of the nucleus |
| Cytokinesis: | Constriction of a contractile ring of actin and myosin filaments at mitotic midzone |
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