Chapter 18: The Cell Division Cycle

Question 1

Name the Four phases of the cell cycle

Answer 1

• G1 phase (Gap 1)
• S phase (synthesis)
• G2 phase (Gap 2)
• M phase (mitosis and cytokinesis)

Question 2

G1 Phase (Gap 1)

Answer 2

Gap 1 phase of the eukaryotic cell cycle
- falls between end of cytokinesis and the start of DNA synthesis

Question 3

S phase

Answer 3

• synthesis
• period during a eukaryotic cell cycle in which DNA is synthesized
• DNA is replicated so there are two copies of each chromosome

Question 4

G2 phase

Answer 4

• Gap 2 phase of the eukaryotic cell cycle
• falls between the end of DNA synthesis and the beginning of mitosis

Question 5

M phase

Answer 5

• mitosis (prophase, prometaphase, metaphase, anaphase, telophase)
• cytokinesis

Question 6

How is the cell cycle regulated

Answer 6

• expression of cyclins and acitivty of different Cdks is regulated at different phases of the cell cycle
• A Cdk must bind to a regulatory protein called cycling BEFORE it can become active
• activation also requires activating phosphorylation of Cdk
• cyclin-Cdk phosphorylates key proteins in cell required to initiate particular steps in cell cycle, directs Cdk to target proteins

Question 7

Describe importance of Gap phases

Answer 7

• cell monitors both internal and external environment
• monitoring ensures conditions are suitable for reproduction and preparations are complete before cell commits to S phase and M phase/mitosis

Question 8

cyclin

Answer 8

• regulatory protein whose concentration rises and falls at specific times during eukaryotic cell cycle
• help control progression from one stage of the cell cycle to next by binding to Cdks

Question 9

Cdks

Answer 9

• cyclin-dependent protein kinases
• enzyme that, when complexed with regulatory cyclin protein, can trigger various events in the cell -division cycle by phosphorylating specific target proteins

Question 10

Describe the Metaphase to Anaphase transition

Answer 10

• metaphase: spindle poles on opposite sides of cell, connected to sister chromatids in middle of cell by mitotic spindles
• anaphase pulls sister chromatids apart to opposite sides of the cell
• transition to get there includes MCdk phosphorylating and activating APC/C
• APC.C ubiquitylates M cyclin
• M cyclin degraded, then MCdl inactivated

Question 11

Describe APC at M phase

Answer 11

• APC places a ubiquitin tag on the M cyclin at the metaphase to anaphase transition
• this causes the M cyclin to be degraded, becomes inactive

Question 12

What does M-Cdk phosphorylate?

Answer 12

• nuclear lamins
• proteins involved in DNA condensation
• proteins involved in making mitotic spindle
• activation of APC/C(degrades M cyclin)

Question 13

Why does M-Cdk phosphorylate nuclear lamins?

Answer 13

• causes breakdown of nuclear envelope

Question 14

Why does M-Cdk phosphorylate proteins involved in DNA condensation and proteins that make the mitotic spindle?

Answer 14

• condensins help pull chromosomes apart
• microtubule binding proteins

Question 15

S-Cdk

Answer 15

• phosphorylates proteins involved in DNA replication
• these are the origin replication complex (ORC) and DNA helicases
• this allows DNA replication so that there is 2X the DNA, so each cell gets a copy after cell division is complete

Question 16

How is the expression of cyclins and activity of Cdks regulated?

Answer 16

• transcription of cyclins
• Ubiquitylation by APC/C
• regulating Cdks directly
• protein binding inhibits activity of some Cdks

Question 17

Transcription of cyclins

Answer 17

• regulates epxression of cyclins
• cyclin regulation
• activated by mitogens, factors that activiated signaling pathways to cause cell division
  RTK -> ras-GEF -> ras GTP -> MAPK -> S-phase cell division

Question 18

Ubiquitylation by APC/C

Answer 18

• regulates expression of cyclins
• causes degradation of cyclins when no longer needed (M cyclin)
• Ubiquitylation of S- or M-cyclin by APC/C marks the protein for destruction in proteasomes
• The loss of cyclin renders its Cdk partner inactive

Question 19

Regulating Cdks directly

Answer 19

• phosphorylation: example MCdk
• protein binding inhibits activity of some Cdks, p21 inhibits G1/S and S Cdks

Question 20

APC/C

Answer 20

• Anaphase promoting complex
• MCdk activates APC/C at the metaphase/anaphase transition
• APC/C then puts a ubiquitin tag on M cyclin
• M cyclin degraded in proteosome, becomes inactive
• phosphate groups put on all of the proteins (lamins, condensins, microtubule binding proteins) that were phosphorylated by MCdk at the start of metphase, are now removed by phosphatases in the cell
• this above process allows nuclear envelope to start reforming, chromatin can start to decondense, mitotic spindle disassembles

Question 21

Describe how M-Cdk is regulated by phosphorylation

Answer 21

• for M-Cdk to be active inhibitory phosphates must be removed
• as soon as the M-Cdk complex is formed, it is phosphorylated at two adjacent sites by an inhibitory protein kinase called Wee1
• modification keeps M-Cdk inactive until phosphates are removed by an activating protein phosphatase called Cdc25

Question 22

Cdk inhibitor proteins

Answer 22

• regulatory protein that blocks the assembly or activity of cyclin-Cdk complexes, delaying progression primarily through G1 and S phases of the cell cycle
• the inhibitory protein binds to activated cyclin-Cdk complex; its attachment prevents the Cdk from phosphorylating target proteins required for progress through G1 into S phase

Question 23

How are sister chromatids separated?

Answer 23

• separate at anaphase
• cohesins are proteins that hold sister chromatids together, degraded in anaphase

Question 24

What do mitogens do in cell cycle?

Answer 24

promote the production of cyclins that stimulate cell division (moving from G1 Phase to S Phase)

Question 25

Describe how mitogens promote proliferation/cell division?

Answer 25

• mitogens stimulate cell proliferation by inhibiting the Rb protein
• Rb usually prevents turning on of genes for cell proliferation by being attached to transcription regulators
• mitogens binding to cell-surface receptors activate intracellular signaling pathways
• this activation activates G1-Cdk and G1/S Cdk complexes
• complexes phosphorylate and inactivate Rb protein, release transcription needed for S phase

Question 26

Describe how DNA damage can halt progression temporarily from G1 to S

Answer 26

• DNA damage in G1 causes increase in concentration and acitivity of protein p53
• p53 activates gene encoding a Cdk inhibitor protein called p21
• p21 binds to G1/S Cdk and S-Cdk, preventing them from driving the cell into S phase
  (gives cell in G1 time to repair damage DNA before replication)

Question 27

p53

Answer 27

• transcription regulator that controls the cell’s response to DNA damage, preventing the cell from entering S phase until the damage has been repaired
• induces cell to unalive itself if the damage is too extensive (apoptosis)
• mutations in gene encoding this protein are found in many human cancers

Question 28

Describe DNA damage checkpoint

Answer 28

• can arrest cell cycle in G1
• specific protein kinases respond by both activating the p53 protein and halting its otherwise rapid degradation
• activated p53 protein thus accumulates and stimulates the transcription of the gene that encodes the Cdk inhibitor protein p21
• p21 binds to G1/S-Cdk and S-Cdk to inactivate them

Question 29

What occurs when DNA damage cannot be repaired?

Answer 29

• apoptosis

Question 30

Describe the trigger of Apoptosis

Answer 30

• Bax and Bak can trigger apoptosis by releasing cytochrome c from mitochondria