FINAL -- pRb control and the Cell Cycle Clock #12

Question 1

The Cell Cycle

Answer 1

• A well-ordered sequence of events that take place in a proliferation cell
• Normal cell growth, development, and maintenance depend on the timing and rate of cell division. It must be tightly regulated
• Phases and checkpoints
• R checkpoint is referring to g1 restriction point and g1 checkpoint

Question 2

Cell Cycle molecular circuitry

Answer 2

• The cell cycle is regulated at checkpoints through a molecular circuitry sensitive to internal & external signals
• The actions of most oncogenes and TSGs can be explained in terms of their effects on the cell cycle
• Cells make decisions about proliferation and quiescence during a specific period in the G1 phase

Question 3

G0 phase

Answer 3

Cells may enter the Go phase prior to the R checkpoint for a variety of reseasons

• If a cell (any cell) has exited the cell cycle, it is usually considered in G0 phase; however, occasionally a distinction is made between a G0 cel

Question 4

Three G0 states

Answer 4

1. Quiescent - resting, inactive - reversible
2. Senescent - not resting or active
3. Differenciated (not inactive.

Question 5

Metaphase checkpoint

Answer 5

Passes through if all chromosomes are attached to the mitotic spindle

Question 6

G1/R checkpoint

Answer 6

• monitors external and internal conditions (DNA) damage

Question 7

S-phase checkpoint

Answer 7

Passes if DNA replication is complete and has been screened to remove a base-pair mismatch error

Question 8

S, G2 and M

Answer 8

• monitors internal conditions

Question 9

G2 checkpoint

Answer 9

Pass is cell size is adequate and chromosome replication is successfully cpmpleted

Question 10

Anaphase can be blocked if…

Answer 10

it is not properly attached to the mitotic spindle

Question 11

Entrance into S is blocked and DNA replication is halted if…

Answer 11

genome is damaged

Question 12

During G1 cells are responsive to:

Answer 12

• Nutrient levels
• Anchorage dependence
• Mitogenic growth factors

Question 13

Choices prior to/at R point:

Answer 13

• Remian in active proliferation
• Exit from cell cycle
  -Apoptosis

Question 14

By passing the R point..

Answer 14

Cells commit to completing the cell cycle independent of extracellular signals.

Question 15

Cyclin CDK complexes

Answer 15

• Constitute the engine of cell cycle clock
• Regulate passage through the checkpoints
• Send signals from the “clock” to the “responder molecules” that carry out the actual work of the cell cycle

Question 16

Cyclin-dependant Kinases

Answer 16

• these kinases are constitutively expressed (and in molar excess), but lack activity until bound by their cognates. Once they are bound to the cyclin, CDKs adopt and active conformation
• Serine/threonine protein kinases phosphorylate key substrates to promote DNA synthesis, mitotic progression, and other mechanisms.

Question 17

Cyclins

Answer 17

• The regulatory subunit of Cyclin-CDK complexes
• Cyclins are tightly regulated at the levels of synthesis and ubiquitin-dependent degradation
• In a pre-programmed/autonomous fashion, cyclin concentrations (except D-type) rise somewhat abruptly, and then fall due to degradation
• Different cycline rise and fall at different times during the cell cycle to control progression through the checkpoints

Question 18

Cyclin-CDK complex formation

Answer 18

• when a cyclin reaches threshold concentration, it binds to its cognate CDK. The CDK then activates proteins through phosphorylation and these proteins drive the cell past the checkpoint and carry out steps in the next phase

Question 19

Cyclin degradation

Answer 19

• Cyclin concentration abruptly drops due to its degradation by the ubiquitin-proteasome pathway. The results in the inactivation of the CDK snd allows the cell to move forward in the cell cycle.

Question 19

How is coordination achieved by cyclin-CDK complexes in one phase of the cell cycle:

Answer 19

• Activating those in the next phase
• Shutting down those active in the previous phase

Question 20

The ubiquitylating protein complex that tags the cyclin with ubiquitin is

Answer 20

activated by the cyclin-CDK itself, so the CDK contributes to its own delayed inactivation
= Negative feedback

Question 21

What drives progression through G1 (the critical decision step)

Answer 21

Cycil D with CDK 4/6

Question 22

D-type cyclins

Answer 22

• extracellular signals strongly influence their levels
• continuously inform the cell cycle clock
• induced by different signals enabling cells to respond to a diverse set of extracellular signals

Question 23

CDK inhibitors

Answer 23

Inhibitors that regulate cyclin-CDK activity provide a mechanism to link environmental signals to cyclin-CDK activity.
- Contol of Cell cycle prgressosion by TGF-beta and DNA damage
- Control of cell cycle by extra cellular signals
- Interactions of CDK inhibitors with cyclin CDK complexes

Question 24

Upon mitogenic stimulation…

Answer 24

Cyclin D is synthesized