BIOL-L 211: Cell Cycle
47 Cards in this Set
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Cell cycle
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series of highly coordinated processes that ensure cell duplication occurs in a precise and timely manner
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G1 phase
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cell growth; no major observable changes in shape or size of chromosomes; essential processes occur throughout
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Start/ restriction point
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G1 checkpoint; once cells have passed they are committed to go through the whole cycle; regulated by external signals
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G0
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Also known as quiescence; non-dividing state sometime occurs during G1; most human cells are naturally arrested in G0
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S phase
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DNA is replicated; duplicated chromosome information forms two sister chromatids bound by protein complex called cohesion
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G2 phase
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cells prepare for chromosome segregation; increase cellular content; mitotic spindle forms
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Mitotic spindle
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apparatus that drives chromosome segregation
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Checkpoint pathways
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monitor integrity of different cellular structures
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M phase
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Chromosome segregation; characterized by specific changes in chromosome organization
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Kinases
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catalyze transfer of phosphate group from a donor to target a protein; regulated by cyclins
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Cyclin-dependent kinases (cdks)
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key regulators of cell cycle progression; enzymes that drive and regulate cell cycle; belong to a family of serine/ threonine protein kinases that phosphorylate specific serine/ threonine residues on substrates
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Cyclins
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Regulatory proteins present at different levels during different cell cycle phases; lead to activation of distinct cyclin-cdk complexes at different stages; lead to conformation change in cdk to activate it
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Cyclin box
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small region of about 100 aas consisting of 5 alpha helices bound to highly conserved motif called PSTAIRE; after binding to PSAIR, major structural changes occur so kinase can adopt active conformation
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Hydrophobic patch
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domain in cyclin that allows some to bind directly to specific substrate
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Phosphorylation and dephosphorylation of cdks
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specific threonine residue adjacent to kinase active site must be phosphorylated; tyrosine residue and adjacent threonine residue must be dephosphorylated
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Cdk-activating kinases (CAKs)
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enzymes that catalyze phosphorylation of threonine to activate cdk; post-translational modification; active throughout cell cycle
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Wee1 kinase
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phosphorylate thr14 and tyr15 in ATP-binding site of cdk; active during G1, S, and G2
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Cdc25
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dephosphorylates thr14 and tyr15 at ATP-beinding site of cdk; active in G2
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Positive feedback loop
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Wee1 inhibited and cdc25 activated by M phase cyclin-cdk phosphorylation; inhibits its inhibitor and activates its activator; presence of positive feedback loop creates an ON/OFF switch
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DNA damage checkpoint pathway
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regulatory pathway that leads to phosphorylation of cdc25 in the presence of DNA damage; inactivates cdc25 so inhibitory phosphorylations at thr14 and tyr15 cannot be removed
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Cyclin kinase inhibitors (CKI)
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specific inhibitory proteins that bind and inactivate cyclin-cdk complexes; two classes
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CKIs that bind to cyclin and cdk
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G1-S or S phase cyclin-cdk complexes; bind to hydrophobic patch of cyclin and large domain of cdk; distort structure and indirectly inhibit ATP binding
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CKIs that bind to G1 cdk monomers on the face of the protein opposite the active site
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induces global change in cdk structure; reduces cyclin binding and alters active site
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E2F
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Transcription factor inhibited prior to restriction point through association with one of Rb family of proteins; Rb targeted by cyclin-cdks for phosphorylation to allow E2F to activate transcription of genes
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Protein degradation
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eliminates proteins needed for previous cell cycle stages to ensure cycle moves forward; cyclin-cdks promote proteolytic destruction of key regulatory proteins
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Ubiquitin-mediated proteolysis machinery
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ubiquitin attachment to protein catalyzed by ubiquitin ligase; targets proteins for degradation
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Proteasome
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large protease complex that destroys proteins targeted by ubiquitination
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SCF complex
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ubiquitin ligase that regulates G1-S transition by degrading specific proteins phosphorylated by G1-S cyclin-cdks; named for skp1, culling, and f-box protein; contains Rbx1
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Rbx1
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RING domain protein in SCF complex; binds to E2 enzyme
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F-box protein
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subunit of SCF complex that binds protein substrate to be ubiquitinated
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Anaphase-promoting complex (APC)
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ubiquitin ligase that drives anaphase and mitotic exit; activated by cdk phosphorylation; targets numerous substrates for degradation during G1; complex of 11-13 subunits including cullin and RING domain
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substrate specificity of APC
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determined by activator subunits; cdc20 and cdh1 are particularly important; cdc20 targets proteins for ubiquitination by APC in early mitosis; cdh1 targets proteins for ubiquitination by APC in late mitosis and G1
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Sensors
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proteins that sense the cellular defect and activate check point response; different types of damage recruit distinct sensors which ensures correct checkpoint pathway is triggered and others remain dormant
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Transducers
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proteins that launch the checkpoint pathway response; protein kinase and proteases are different types; can activate multiple effectors simultaneously
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Effectors
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group of proteins that actually carry out checkpoint pathway response
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Spindle assembly checkpoint pathway
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monitors attachment of chromosomes to spindle to ensure proper segregation; main effector is APC
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Mitogens
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promote passage through the restriction point; activate cell cycle machinery; directly stimulate cells to divide and proliferate without stimulating growth; generally soluble peptides or small proteins secreted by neighboring cells
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Growth factors
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molecules that stimulate cells to increase their mass; stimulate division indirectly
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TOR
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protein kinase that regulates growth rate
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Epidermal growth factor (EGF)
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mitogen; soluble polypeptide that controls initiation of division in many different cell types; directly stimulates entry to cell cycle at G1
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Primary changes that fuel cancer growth
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1Dominant activation of extrinsic signaling pathways 2Loss of regulatory mechanisms 3Genetic alterations that allow accumulation of multiple mutations
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Oncogenes
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promote tumor growth
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Tumor suppressor genes
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normally halt cell cycle but fail to do so in cancer
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Autocrine loop
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stimulates cell to promote its own division as well as that of its surrounding cells
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Bacterial cell cycle
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B period: bacterium increases in mass and size
C period: DNA replication and chromosome segregation take place
D period: time between end of DNA replication and subsequent cell division
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Multifork replication
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occurs when a new round of replication begins before previous one has been complete
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SOS response
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induces transcription of DNA repair genes and inhibits cell division in bacteria; binding of protein RecA to ssDNA results in activation of proteolytic activity that cleaves and inactivates a transcription repressor called LexA
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BIOL-L 211: DNA REPLICATION