Ch.18 - Cell Division Cycle Flashcards Preview

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Flashcards in Ch.18 - Cell Division Cycle Deck (97)
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1

The euk CC typ incl wh four phases? Briefly summarize.

M Phase - nuclear division (mitosis) and cell splitting in two (cytokinesis).

Interphase - period b/w M phases; comprised of G1, S, and G2 phases.

  • S phase - DNA repl; cytoplasmic organelles (incl centrosome) also duplicated.
  • G1 & G2 - gap/growth; cell monitors IC/EC environ to ensure favorable conditions; also checks that prep is complete.

2

T/F: During all of interphase, gene xcr typ continues.

True

During all of interphase, gene xcr typ continues → proteins synthd → cell grows.

  • G1 and G2 phases are nearly absent during some embryonic CC's; cell div (prolif) occurs v rapidly.

3

The euk ___________________ is a complex network of regulatory proteins that helps ensure cells repl all DNA/organelles and divide in orderly manner.

Euk cell-cycle control system (CCCS) is a complex network of regulatory proteins that helps ensure that cells repl all DNA/organelles and divide in orderly manner.

  • Guarantees CC (DNA repl, mitosis, etc.) occur in set seq and that ea process completed before next one begins.

4

CCCS is itself regulated at certain critical points by feedback. How does slowed/stalled DNA synth, such as due to DNA damage, impact the rest of the CC?

If DNA synth is slowed/stalled → mitosis and CD must also be delayed.

  • If DNA is damaged → CC must arrest in G1, S, or G2 so cell can repair damage, either before DNA repl is started/completed or before cell enters M phase.
  • CCCS employs molecular brakes ("checkpoints") to pause CC at certain transition points → prevents trigger of next step unless/until cell is properly prepared.

5

CCCS regulates progression thru CC at wh three main transition points?

CCCS regulates progression thru CC at three main transition points.

G1 to S phase - before committing to DNA repl, CCCS confirms that IC/EC environ is favorable for prolif.

  • Partic imp in animal cells - cell prolif in animals reqs both sufficient nutrients (IC) and specific signals (EC).
  • If conditions unfav → cell can transiently delay progress thru G1; may even enter G0.

G2 to M phase - before entering mitosis, CCCS confirms DNA is undamaged (i.e. intact) and fully repl.

During mitosis - before spindle pulls chromos apart/segr into daughter cells (anaphase), CCCS ensures dupl chromos are properly attached to mitotic spindle.

6

The core of CCCS is a series of molecular ______ that operate in a defined seq and coord main events of CC, incl _______ and ____________.

The core of CCCS is a series of molecular switches that operate in a defined seq and coord main events of CC, incl DNA repl and segr of dupl chromos.

7

CCCS governs CC machinery by cyclically in/activating key proteins/complexes that initiate or regulate DNA repl, mitosis, and cytokinesis. This regulation is carried out largely thru ________________ of regulatory proteins.

CCCS governs CC machinery by cyclically in/activating key proteins/complexes that initiate or regulate DNA repl, mitosis, and cytokinesis. This regulation is carried out largely thru de/phos of regulatory proteins.

8

T/F: Protein kinases at core of CCCS are present in proliferating cells thru/o CC.

True

Protein kinases at core of CCCS are present in proliferating cells thru/o CC; activated, h/e, only at partic times in CC, after wh they are quickly inactivated.

  • Activity of ea CCCS kinase rises/falls in cyclical fashion.
  • Recall: switching on/off CCCS kinases is also partly regulated by cyclins; hence "cyclin-dep protein kinases" (Cdks).

9

The concen of both cyclin-dep protein kinases (Cdks) and cyclins rises/falls in cyclical fashion during CC.

False

The activity of Cdks and concen of cyclins rises/falls in cyclical fashion.

  • I.e. Cdks are present thru/o CC, but activated only at partic times, then quickly inactivated.

10

As S cyclin concen ↑ → ______ (concen/activation) of S-Cdk __ (↑/↓) → drives cell into ___ phase.

As S cyclin concen ↑ → activation of S-Cdk  → drives cell into S phase.

11

Diff cyclin–Cdk complexes trigger diff steps of CC. Describe the activity of four cyclin-Cdk complexes, incl when active and effect on CC.

M cyclin - acts in G2 to trigger entry into M phase; forms active complex (M-Cdk) w specific Cdk.

S cyclins and G1/S cyclins also bind distinct Cdks late in G1 to form S-Cdk and G1/S-Cdk, resp → help launch S phase.

G1 cyclins - act earlier in G1, bind other Cdks to form G1-Cdks → help drive cell thru G1 toward S phase.

  • Formation of these G1-Cdks in animal cells typ deps on EC signals that stim cell to divide.

Each cyclin–Cdk complex phos's diff set of target proteins in cell; e.g. G1-Cdks phos regulatory proteins that activate xcr of genes reqd for DNA repl.

  • By activating diff sets of target proteins, ea type of complex triggers diff transition step.

12

T/F: ea cyclin–Cdk complex phos's diff set of target proteins in cell.

True

Each cyclin–Cdk complex phos's diff set of target proteins in cell.

  • E.g. G1-Cdks phos regulatory proteins that activate xcr of genes reqd for DNA repl.
  • By activating diff sets of target proteins, ea type of complex triggers diff transition step.

13

Cyclin concens are regulated by ________ and ________. Over the course of CC, concen of ea cyclin rises _______ (abruptly/gradually) then falls _______ (abruptly/gradually).

Cyclin concens are regulated by xcr and proteolysis. Over the course of CC, concen of ea cyclin rises gradually then falls abruptly.

  • Gradual ↑ in cyclin concens stems fr ↑ xcr of cyclin genes.
  • Rapid ↓ in cyclin concens is precipitated by a full-scale targeted destruction of the protein via ubiquitylation by anaphase-promoting complex (APC).

14

The gradual ↑ in cyclin concens stems fr ↑ xcr of cyclin genes. By contrast, the rapid ↓ in cyclin concens is precipitated by a full-scale targeted destruction of the protein via ____.

Gradual ↑ in cyclin concens stems fr ↑ xcr of cyclin genes.

Rapid ↓ in cyclin concens is precipitated by a full-scale targeted destruction of the protein via ubiquitylation by anaphase-promoting complex (APC).

  • Abrupt degrad of M and S cyclins partway thru M phase deps on large enzyme complex (APC), wh tags M and S cyclins w chain of ubiquitin (ubiquitylation) → cyclin degrad → Cdk returns to inactive state → helps drive transition fr one CC phase to next.
    • e.g. M-cyclin degrad → inactivatopm of M-Cdk → cell taken out of mitosis.

15

Cyclin concens ↑ gradually, but activity of cyclin-Cdk complexes tends to switch on abruptly. Describe the mechanism by wh cyclin-Cdk complexes are activated.

Cyclin–Cdk complexes contain inhibitory P's→ must be dephos by specific protein phosphatase to become active.

E.g. as soon as M-Cdk complex formed → phos'd at two adj sites by an inhibitory protein kinase (Wee1) → keeps M-Cdk inactive until Pi's are removed by an activating protein phosphatase (Cdc25)

  • Note only one of two phos'd site shown in Fig.
  • Still not clear how timing of Cdc25 phosphatase is controlled.

16

Explain how both protein kinases and phosphatases regulate activity of specific cyclin–Cdk complexes → control CC progression.

Cyclin-dep protein kinases (Cdks) are at the core of CCCS; present thru/o CC, but activity rises/falls in cyclical fashion.

Switching Cdks on/off is partly regulated by cyclins, whose concen rises/falls in cyclical fashion.

Cyclin-Cdk complexes are phos'd—and inhibited—at two sites by Wee1 shortly after formation → inactive until Cdc25—an activating protein phosphatase—dephos's both inhibitory P's.

17

In addition to de/phos, activity of Cdks can also be modulated by binding of _________ proteins, such as ___.

In addition to de/phos, activity of Cdks can also be modulated by binding of Cdk inhibitor proteins, such as p27.

  • Inhibitors can block assembly/activity of certain cyclin–Cdk complexes.
  • p27 binds an activated cyclin-Cdk complex → prevents Cdk fr phos'ing target proteins reqd for progression thru G1 into S phase.
    • i.e. p27 maintain Cdk in inactive state during G1 phase → delay progression into S phase and provide more time for cell growth or more favorable EC conditions.

18

Describe the function of p27 in the CCCS.

p27 binds an activated cyclin-Cdk complex → prevents Cdk fr phos'ing target proteins reqd for progression thru G1 into S phase.

  • i.e. p27 inactivate Cdk during G1 phase → delay progression into S phase and provide more time for cell growth or more favorable EC conditions.

19

CCCS uses a combo of mechanisms to transiently delay progress at transition points and ensure proper conditions and set seq of events. Describe the mechanisms that can be activated at three major transition points.

At G1-to-S transition, Cdk inhibitors (p27) can prevent cells fr entering S phase and replicating their DNA; i.e. waits for favorable IC/EC conditions or until DNA damage repaired.

At G2-to-M transition, can inhibit activating phosphatase (Cdc25) reqd to activate M-Cdk; i.e. triggers mitosis only after DNA completely repl.

At exit fr mitosis, can inhibit activation of APC → prevents ubiquitylation & degrad of M cyclin; i.e. initiates chromo sep only after dupl chromos correctly aligned on mitotic spindle.

20

Why is the G1 to S phase transition such an imp checkpoint?

G1 is an imp checkpoint: based on IC signals (cell size) and EC signals (growth factors), CCCS can either hold cell transiently in G1 (or G0) or allow prep for entry into S phase of another CC.

  • Beyond this critical G1-to-S transition, cell typ progresses thru rest of CC quickly—typ w/i 12–24 hours in mammals.
    • In yeasts, G1-to-S transition sometimes called "Start", bc passing it reps commitment to a full CC

21

Cdks are stably ________ (in/activated) in G1.

Cdks are stably inactivated in G1.

Recall: during M phase, cells are actively dividing and awash w active cyclin–Cdk complexes (S-, M-Cdks). These complexes must be inactivated by end of M phase, or cell will immediately repl DNA and initiate another round of division, w/o spending any signif time in G1 or G2 phases.

  • Cdk inhibitor proteins (e.g. p27) bind/inactivate cyclin Cdk complexes.
  • APC ubiquitylates cyclin → cyclin degrads → Cdk inactivated.
  • Synth of new cyclins is also blocked.

22

Why do you suppose cells have evolved a special G0 phase, rather than just stopping in G1 and not moving on to S phase?

For multicell orgs, control of CD is v imp. Individual cells must not prolif unless it is to benefit whole org. G0 offers protection fr aberrant activation of CD, bc CCCS is largely dismantled.

Alt, if cell just paused in G1, it would still contain all CCCS and could readily be induced to divide. The cell would also have to remake the “decision” not to divide almost continuously. To re-enter CC fr G0, cell has to resynth all components that have disappeared.

23

Typ, mammalian cells will multiply only if stim'd by ___ (IC/EC) signals, such as _______, produced by other cells.

W/o prolif signals → CC arrests in ___ phase.

W/o prolif signals for long period → cell withdraws fr CC and enters ___.

Typ, mammalian cells will multiply only if stim'd by EC signals (mitogens) produced by other cells.

W/o EC prolif signals → CC arrests in G1.

W/o EC prolif signals for long period → cell withdraws fr CC and enters nonprolif state (e.g. G0) for variable time.

24

Escape fr CC arrest or certain non-prolif states reqs accumulation of ______.

Escape fr CC arrest or certain non-prolif states reqs accumulation of cyclins.

Mitogens switch on signal paths that stim synth of G1 cyclins, G1/S cyclins, and other proteins involved in DNA synth/chromo dupl → buildup of cyclins triggers wave of G1/S-Cdk activity → relieves negative controls (block progression fr G1 to S phase).

25

Escape fr CC arrest or certain non-prolif states reqs accumulation of cyclins. _______ switch on signal paths that stim synth of G1 cyclins, G1/S cyclins, and other proteins involved in DNA synth/chromo dupl → buildup of cyclins triggers wave of ________ activity → relieves ____ (neg/pos) controls—that is, it blocks progression fr __ to __ phase.

Escape fr CC arrest or certain non-prolif states reqs accumulation of cyclins. Mitogens switch on signal paths that stim synth of G1 cyclins, G1/S cyclins, and other proteins involved in DNA synth/chromo dupl → buildup of cyclins triggers wave of G1- and G1/S-Cdk activity → relieves neg controls—that is, it blocks progression fr G1 to S phase.

  • E.g. Retinoblastoma (Rb) - rare childhood eye tumor; Rb protein is missing/defective.

26

Retinoblastoma (Rb) is a rare childhood eye tumor in wh Rb protein is missing/defective. In dephos state, Rb binds/inhibits partic xcr regulators that normally turn on genes reqd for cell prolif. Describe what happens when EC signals like mitogen bind a cell w normal Rb as well as one w Rb missing/defective.

In dephos state, Rb binds/inhibits partic xcr regulators that normally turn on genes reqd for cell prolif; i.e. negative control.

Recall enzyme-coupled receptors & RTKs: in active state, Ras initiates phos cascade → ser/thr protein kinases phos/activate one/an in seq → activates mitogen-activated protein kinase (MAP kinase) signal path.

In cell w normal Rb: mitogens trigger activation of G1- and G1/S-Cdks → phos/inactivate Rb → Rb changes conform and releases bound xcr regulator → xcr regulator free to activate genes reqd for cell prolif, thus relieving Rb "brake"/neg control.

In cell w missing/defective Rb: mitogens trigger activation of G1- and G1/S-Cdks → Rb not present → xcr regulator unbound and continuously activates genes reqd for cell prolif.

27

In repsonse to DNA damage in G1, specific protein _______ (kinases/phosphatases) _______ (in/activate) p53—a xcr regulator—and halt its ______ (synth/degrad) → p53 ________ (in/activates) xcr of gene encoding p21, a Cdk inhibitor → p21 binds ___-Cdk and ___-Cdk and prevents them fr driving cell into S phase → cell arrests in ___ → cell repairs damaged DNA before repl.

In repsonse to DNA damage in G1, specific protein kinases activate p53—a xcr regulator—and halt its degrad (↑ p53 concen) → p53 activates xcr p21, a Cdk inhibitor → p21 binds G1/S-Cdk and S-Cdk and prevents them fr driving cell into S phase → cell arrests in G1 → cell repairs damaged DNA before repl.

  • If DNA damage is beyond repair, p53 can induce apoptosis (see later).
  • If p53 missing/defective → unrestrained repl of damaged DNA → high rate of mutation/cancer.
  • If protein kinases that normally phos/activate p53 are blocked → damaged DNA replicated.

28

p53—a xcr regulator—is stabilized and activated by protein kinases in response to DNA damage. What happens to the IC concen of p21 when p53 is activated? What happens if DNA damage is beyond repair, or if p53 is missing/defective?

DNA damage in G1 → specific protein kinases activate p53—a xcr regulator—and halt its degrad (thus, ↑ p53 concen) → p53 activates xcr of gene encoding p21, a Cdk inhibitor → p21 binds G1/S- and S-Cdk and prevents them fr driving cell into S phase → cell arrests in G1 → cell repairs damaged DNA before repl.

  • If DNA damage is beyond repair, p53 can induce apoptosis.
  • If p53 missing/defective → unrestrained repl of damaged DNA → high rate of mutation/cancer.

29

Cells can delay division for prolonged periods by temporarily or permanently entering specialized non-dividing states. What causes cells to enter such a state, and in what types of cells is this desirable?

Many human cells (e.g. nerve/muscle) permanently stop dividing when they differentiate → completely dismantles CCCS and irreversibly shuts down genes encoding relevant cyclins/Cdks.

In absence of approp signals, other cell types withdraw fr CC only temporarily → enter arrested/quiescence state: G0.

  • Cells in G0 retain ability to reassemble CCCS quickly and divide again; e.g. most liver cells are in G0, but can be stimulated to prolif if liver is damaged.

30

T/F: cells in G0 retain ability to reassemble CCCS quickly and divide again.

True

Cells in G0 retain ability to reassemble CCCS quickly and divide again; e.g. most liver cells are in G0, but can be stimulated to prolif if liver is damaged.

Alt, many human cells (e.g. nerve/muscle) permanently stop dividing when they differentiate → completely dismantles CCCS and irreversibly shuts down genes encoding relevant cyclins/Cdks.