Regulation Of Cell Cycle Flashcards
G1 phase
. RNA and protein synthesis
. Growth from organelle and intracellular structure duplication
. Length of phase variable among cells (rapidly dividing cells spend less time than mature cells that stay in it permanently)
G0 phase
. Cells in G1 phase that are not committed to DNA synthesis
. Some inactive or quiescent cells in this phase can reenter active phases upon proper stimulation
Restriction point
. Time point in G1 that if passed will commit cell to continuing into DNA synthesis w/in S phase
. Critical for cell cycle regulation
G2 phase
. Btw S and mitosis
. Safety gap that allows cell to ensure DNA synthesis is complete before going into mitosis
. Has checkpoint where intracellular regulatory molecules assess nuclear integrity
. Lasts about 4 hrs
How long is mitosis
1 hour
Prolapse
. Nuclear envelope intact
. Chromatin condenses
. Kinectochores assoc. w/ each chromatid
. Mitotic spindle microtubules attach to each kinectochore
. Microtubules of cytoplasm disassemble then reorganize on surface of nucleus to form spindle
. 2 centriole pairs push away from each other by growing bundles of microtubules
. Nucleolus disassembles
Prometaphase
. Disassembly of nuclear envelope
. Spindle microtubules bind to kinectochores and chromosomes are pulled by microtubules
Karyotype analyses require cells to be in what phase of mitosis?
Metaphase
Anaphase
. Mitotic poles pushed from polar microtubules elongating
. Centromeres split in 2
. Paired kinectochore separate
Telophase
. Last phase nuclear division
. Kinetochore microtubule disassembly and mitotic spindle dissociation
. Nuclear envelopes form around each of 2 nuclei containing chromatids
. Chromatids de-condense into dispersed chromatin and nucleoli reform
Cytokinesis
. Actin microfilament ring forms
. Contraction of structure causes cleavage seen in beginning of anaphase
. Plasma membranes fuse of each side of furrow resulting in 2 cells
Senescent cells
. Cells that have permanently stopped dividing due to age or accumulated DNA damage
Hepatocytes in regards to cell division
. Do not continuously reverse cell cycle like intestinal epithelial cells, but retain ability to go through it
. Reason why partial livers can be transplanted
Major types of cell cycle mediators
. Cycling
. Cycling-dependent kinases (CDKs)
Cyclins
. Cell cycle regulatory protein
. G1 phase: D-type (1-3): critical for progression through restriction point
. S phase: E cyclins and cyclins A
. Mitotic: cyclins B and A
Cylinder-dependent kinases
. Present in constant amounts during cell cycle
. Activity fluctuates based on cyclin concentrations
. Cyclins complex w/ these to stimulate kinase activity
. Phosphorylates target proteins that cause cell to be driven into S or M phase
. CDK2 drives cell through S phase
. CDK1 drives cells through M phase
. CDK 4 and 6 drive cells past restriction point
G1 checkpoint
. RB protein halts cell in G1 phase
. RB protein has few phosphorylated AA in resting state which prevents entry into S phase by binding to TF E2F that is critical for G1/S phase transition
.p53 stimulates transcription of CDK inhibitor (p21) which halts cell cycle for DNA repair
. If damage is irreparable p53 trigger apoptosis
P53 functions by ____
. Regulating cell cycle control genes
. Arresting cell cycle when DNA is damaged
. Committing cells to apoptosis when DNA damage is too great
CDK inhibitors
. INK4A family inhibits D-type cyclins from assoc. w/ CDK 4 and 6
. CIP/KIP family inhibits CDK2 kinases (p21 part of this family)
G2 checkpoint regulation
. CDK 1 activity controls entry into mitosis
. Inhibitory phosphates removed so CDK1 can bind to cyclin B and stimulate progression through remainder of cell cycle
Cell-cycle specific chemo
. Used for tumors w/ high percentage of dividing cells
. Normal cycling cells also damaged
Antimetabolites
. Compounds structurally related to normal cellular components
. Exert toxic effects on cells in S phase
. Mechanism involves inhibition of synthesis of purine/pyrimidine nucleotide precursors
. Compete w/ nucleotides in DNA and RNA synthesis
. Drugs: methotrexate and 5-fluorouracil
Anti cancer antibiotics
. Cause cells to accumulate in G2 (bleomycin)
. Others impact actively cycling more than resting cells but are not specific to stage by interacting w/ DNA and disrupting DNA function
Mitotic spindle poisons
. Inhibit M phase cells during metaphase
. Binds to tubulin and disrupts spindle apparatus of microtubules required for chromosome segregation
. Used to treat high growth fraction cancers like leukemia
. Drugs: vincristine and vinblastine and taxol
. Taxol: used in combo w/ other chemo drugs to treat metastatic breast cancer, ovarian, and testicular cancer
