Cell Cycle

Question 1

G1/S Checkpoint

Answer 1

• -start or restriction point

- - cell determines if conditions are favorable for division

Question 2

G2/M Checkpoint

Answer 2

–check is made to ensure that all DNA has been replicated and that the environment remains favorable for division

Question 3

Metaphase/Anaphase Transition Point-

Answer 3

–all of the chromos are evaluated to ensure that they are attached to mitotic spindle

Question 4

DNA damage checkpoint

Answer 4

–functions throughout cell cycle to evaluate if there is any DNA damage that is to be repaired

Question 5

Cell Cycle Phases and Associated Cyclins and CDKS’

Answer 5

• -M: Cyclin A and B w/ CDK1
• -Mid G1: Cyclin D w/ both CDK 4 and CDK 6
• -Late G1: Cyclin E w/ CDK2
• -S: Cyclin A w/ CDK2

Question 6

CDK’s

Answer 6

• -cyclin dependant kinases
• -serine, threonine kinases that function w/ cyclins
• -regulate cell progression throughout cycle through phosphorylation of different protein targets

Question 7

mitogenic signals

Answer 7

• -needed for cell to stimulate growth and division
• -most cells in G0
• -mitogenic signals must overcome cycle inhibition barriers such as restriction point

Question 8

Cell division or no division

Answer 8

• -cell-extracelluar matrix interactions usually promote cell division
• -cell-cell interactions usually inhibit cell proliferation

Question 9

Growth Factors

Answer 9

–allow cells to pass restriction point
–stimulate transcription of early response genes (transcription factor c-Fos)
–c-Fos stimulates transcription of delayed response genes (some are transcription factors others are mid-G1 cyclins and CDKS
and late-G1 cyclins

Question 10

Growth Factors bind to receptors on cell surface and what occurs?

Answer 10

• -tyrosine kinase activity of receptor autophosphorylates itself and dimerizes
• • singaling complex then forms at -P of receptor
• -GRB2 binds to -P and then binds Sos protein
• -Sos recruits small G-protein called Ras and activates it by exchanging GDP for GTP
• -Active Ras then activates protein kinase Raf
• -Active Raf then phosphorylates and activates MAP kinase kinase
• -Active MAP kinase kinase phosphorylates and activates MAP kinase which enters nucleus and regulates transcription of many genes

Question 11

Activation of MAP kinase by? and what is outcome?

Answer 11

• -phosphorylated by MAP kinase kinase
• -goes into nucleus and stimulates c-Fos transcription
• -c-Fos helps lead to progression through restriction point

Question 12

After progression past restriction point

Answer 12

–growth factors not needed

Question 13

G1/S Regulation

Answer 13

• -cyclinD/CDK4/6 phosphorylates Rb (retinoblastoma protein) which frees E2F protein (delayed response protein)
• -free E2F stimulates transcription of cyclin E and A and CDK2 readying the cell for transition to S stage

Question 14

When Rb is bound to E2F, E2F is functioning as transcription repressor why?

Answer 14

• -b/c Rb is also bound to histone deacetylases and methylases
• -condensing chromosomes

Question 15

INK4’s

Answer 15

• -growth inhibitory factors

- -compete w/ cyclin D for binding to CDK4/6

Question 16

Regulation of entry into S phase

Answer 16

• -CyclinA/CDK2 is in inhibited state bound to p27KIP1
• -inhibitor is phosphorylated by cyclinE/CDK2 and is ubiquitinated
• -cyclinA/CDK2 is dephosphorylated and once active it will phosphorylate ORC’s to promote DNA replication

Question 17

G2/M Phase Regulation

Answer 17

• -CyclinA/B:CDK1 is inactive due to -P’d on CDK1 until ALL DNA has been replicated
• -CDK1 de-P’d and then cyclinA/B:CDK1 phosphorylate lots of protein substrates to assist w/ chromo condensation, and other events that are responsible for driving the early part of mitosis

Question 18

Anaphase Promoting Complex

Answer 18

• -activated by arrangement of chromos and attachment to mitotic spindle in metaphase
• -complex particpates in chain of events that leads to degradation of cohesin complexes that hold sister chromatids together

Question 19

ATM protein kinase: G2/M Checkpoint

Answer 19

• -detects replication forks
• -if it finds forks, it activates another kinase which goes to prevent de-P and activation of cyclin/CDK1 complexes needed to enter mitosis

Question 20

Metaphase/Anaphase Transition Point Mechanism

Answer 20

• -protein factors recognize kinetochores that arent associated w/ spindle and initiate a sequence leading up to inhibition of anaphase promoting complex function
• -anaphase dependant upon association of all chromos w/ spindle

Question 21

ATM/ATR Dual function

Answer 21

• -ATM activated in response to double DNA strand breaks
• -ATR activated in response to UV light and drug DNA damage
• • work together to inhibit phosphatases from de-P’ing CDK2 and CDK1 cyclins so cell cycle progression is blocked
• -

Question 22

Role of p53

Answer 22

• -activated by active ATM/ATR
• -transcription factor
• -ATM/ATR stabilize it by -P it
• -once stable it will affect transcription of many genes
• -ex. p21CIP1–inhibitor or cyclin dependant kinases (both CDK1 and CDK2 cyclin complexes)
• -DNA damage blocks transition from G1 to S or from G2 to M

Question 23

Ataxia Telangiectasia

Answer 23

–rare inherited disorder
–effects in nervous/immune systems
–difficulty in movement and telangiactasia = small widened blood vessels
–at risk of developing leukemias and lymphomas
–highly sensitive to radiation (X-rays)
–caused by mutations in ATM protein kinase
–no cellular response to double stranded DNA breaks
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