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_____ (x4) are significant purposes of cell proliferation.
- Growth of multicellular organism
- Produce new organisms in unicellular species
- Generation of offspring
- Renew aging, apoptotic cells, and damaged tissue
_____ and ____ are the overall control mechanisms of cellular replication.
Regulation of the timing of nuclear DNA replication and mitosis
_____ are the master controllers of DNA replication and mitotic timing.
- Small number of heterodimeric protein kinases
- Cyclin and cyclin dependant kinase
A checkpoint is _____ and can be from an ____ or _____ signal.
- Stop/Go signal
- internal or external
_____ is an example of an internal checkpoint signal.
Kinotochores not attached to spindle microtubules - triggers molecular signal that delays anaphase.
____ is an example of an external checkpoint signal.
Growth factors - stimulate transduction machinery that regulates trx of replicative and mitotic proteins.
Density-inhibition is _____.
Anchorage-dependance is _____.
- Different ways of regulation the cell cycle
- Density-inhibition: crowded cells stop dividing (Confluence)
- Anchorage-dependance: Cell must be attached to a substratum (Most animal cells)
There is a diffusable factor present in _____ cells which causes _____ in cells that come into contact with it.
- Mitotic cells
- Nuclear envelope retraction during G1 phase cells and chromosome condensation
_____ are the cell cycle phases which are composed of _____ subphases.
- Interphase: G1 S and G2 (90% of cell cycle)
- Mitotic phase: Prophase, Prometaphase, Metaphase, Anaphase, Telophase/Cytokenisis
The cell cycle control system is similiar to a _____ and is regulated by _____ and _____ controls. ____ is the most important checkpoint resulting in _____ if given the "go ahead" or _____ if the cell does not recieve the "go-ahead" signal.
- Internal and External
- late G1; completion of S, G2, and M phases and will divide or enter G0 phase
MPF is _____ that is responsible for _____.
Maturation Promotion Factor is a Cyclin CDK complex that is responsible for cell passage past G2 checkpoint into M phase.
A cyclin is a _____. Cyclins work by ____.
- Any protein whose concentration rises and falls during the Eukaryotic cell cycle.
- Forming a complex with CDK, activating them, and determining their substrate speceficity.
_____ are the 3 types of regulators for CDK activity.
- Inhibitory proteins
- Ubiquitin-Protein ligases
____ which, _____, is responsible for S-phase initiation.
- SCF (Skp, Cullin, F-box containing complex), which is a ubiquitin protein ligase that marks s-phase inhibitors p27 and p21 for degredation.
- (p21, 27 are cCDK inhibitors)
_____ are the 3 early steps of mitosis and are activated by _____ during _____ phase.
- Nuclear envelope breakdown
- Remodeling of mitotic spindle
- Chromosome condensation
- Mitotic cyclin-CDK's
- Late G2
_____ is responsible for allowing chromosomes to seperate during anaphase and works by ____.
- Polyubiquinating securin
MPF is a/an _____.
Cyclin-CDK heterodimer that is the KEY factor in regulating the initiation of Mitosis in all Eukaryotes
Describe regulation of Mitotic cyclin levels.
- [MPF] high = s phase to M phase. At Metaphase APC/c polyUBq Securin = chromosome seperation.
- Successful chromosomal seperation = cdc14 activation
- cdc14 activation = dephosphorylation of cdh1 = activation of APC/c polyUBq of MPF = [MPF] down = telophase begin
Rb is a/an ____ and prevents the cell from _____ by _____.
- Tumor supressor and prevents the cell from
- replicating damaged DNA by
- preventing the cell from progressing from G1 to S phase.
Rb regulates the cell cycles specifically by _____.
Inhibiting E2F (Rb is an inhibition prot. When bound to E2F it is inactive)
Rb is inactivated by _____.
Phosphorylation by cCDK complex
E2F is a/an _____ and is responsible for _____. E2F is part of a ____ feedback loop
- Transcription factor
- Activating genes required for entry into S phase
Describe mechanism for control of S-phase onset.
- S-phase cCDK's are inhibited by prot Sic1.
- [G1 cCDK] increases until there are enough to phosphorylate Sic1.
- Phosphorylation of Sic1 marks it for polyUbq and proteosomal degredation = S- phase cCDK activation.
The mitotic spindle is _____.
An accumulation of microtubules that control chromosome movement during mitosis
The centrosome is _____.
The originating site of the microtubules for for mitosis
_____ is a ____ that holds together sister chromatids.
- A multiprotein complex
Cohesins work by _____.
- Surround Chromatin and when duplicate DNA is made the helicase passes through the cohesin so both chromatids are inside the cohesin.
- All cohesins release after G2 accept for a few at the center near the centromere.
_____ is the shortes phase of Mitosis and begins when ____ allowing ____.
- Cohesin proteins are cleaved
- Kinotochre microtubules to shorten - pulling Chromatin toward opposite poles
Describe mechanism of Cohesin cleavage
- Seperase is bound by inhibitor protein Securin.
- When spindle apparatus is properly assembled cdc20 activates APC/c polyUBq activity for Seperase
- Seperase is activated and Cohesin is cleaved from Chromatids
The nuclear Lamina is comprised of _____ which are comprised of __#__ lamins and arranged in _____ sets of IF. The lamina is broken down by _____.
- A meshlike network of Lamina intermediate filaments
- 3 Laminas: A, B, and C
- 2 perpendicular sets of IF
- MPF phosphorylates specific serine residues in all three laminas which causes them to depolimerize and the disintegration of the nuclear lamina.
p53 is _____ which also means it is a _____ and is commonly called the "____" because it ____ (x3).
- Tumor suppressor protein which means it is a trx factor and is commonly called the "gaurdian of the genome" because it:
- Activates DNA repair protein
- Inhibits cell cycle at G1/S regulation point
- Initiates apoptosis if DNA is irreparably damaged.
_____ activates p53. Examples of this include _____.
- Cellular stress
- Enviornmental : UV, Chemical agents damaging DNA
- Anything that compromises the cell genetic integrity.
_____ are the three proteins that p53 activates and their role in cell cylce hault.
- p21, p27, p57 AKA CIP's (CDK Inhibiter Proteins)
- They inhibit A-CK2 activity by binding to CDK's and must be degraded before replication can begin.
Disregulation of p53 can be seen in the rare disease _____ where p53 is cannot be exported from the nucleaus for degredation by _____ because of a mutation in _____.
- Taxia Telangiectasia Mutated (ATM/ATR)
- MDM2 and MDMX
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