Regulation Of Cell Cycle

Question 1

G1 phase

Answer 1

. 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)

Question 2

G0 phase

Answer 2

. 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

Question 3

Restriction point

Answer 3

. Time point in G1 that if passed will commit cell to continuing into DNA synthesis w/in S phase
. Critical for cell cycle regulation

Question 4

G2 phase

Answer 4

. 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

Question 5

How long is mitosis

Answer 5

1 hour

Question 6

Prolapse

Answer 6

. 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

Question 7

Prometaphase

Answer 7

. Disassembly of nuclear envelope

. Spindle microtubules bind to kinectochores and chromosomes are pulled by microtubules

Question 8

Karyotype analyses require cells to be in what phase of mitosis?

Answer 8

Metaphase

Question 9

Anaphase

Answer 9

. Mitotic poles pushed from polar microtubules elongating
. Centromeres split in 2
. Paired kinectochore separate

Question 10

Telophase

Answer 10

. 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

Question 11

Cytokinesis

Answer 11

. 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

Question 12

Senescent cells

Answer 12

. Cells that have permanently stopped dividing due to age or accumulated DNA damage

Question 13

Hepatocytes in regards to cell division

Answer 13

. Do not continuously reverse cell cycle like intestinal epithelial cells, but retain ability to go through it
. Reason why partial livers can be transplanted

Question 14

Major types of cell cycle mediators

Answer 14

. Cycling

. Cycling-dependent kinases (CDKs)

Question 15

Cyclins

Answer 15

. 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

Question 16

Cylinder-dependent kinases

Answer 16

. 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

Question 17

G1 checkpoint

Answer 17

. 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

Question 18

P53 functions by ____

Answer 18

. Regulating cell cycle control genes
. Arresting cell cycle when DNA is damaged
. Committing cells to apoptosis when DNA damage is too great

Question 19

CDK inhibitors

Answer 19

. INK4A family inhibits D-type cyclins from assoc. w/ CDK 4 and 6
. CIP/KIP family inhibits CDK2 kinases (p21 part of this family)

Question 20

G2 checkpoint regulation

Answer 20

. 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

Question 21

Cell-cycle specific chemo

Answer 21

. Used for tumors w/ high percentage of dividing cells

. Normal cycling cells also damaged

Question 22

Antimetabolites

Answer 22

. 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

Question 23

Anti cancer antibiotics

Answer 23

. 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

Question 24

Mitotic spindle poisons

Answer 24

. 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