Chapter 18: The Cell Division Cycle Flashcards
1
Q
Name the Four phases of the cell cycle
A
- G1 phase (Gap 1)
- S phase (synthesis)
- G2 phase (Gap 2)
- M phase (mitosis and cytokinesis)
2
Q
G1 Phase (Gap 1)
A
Gap 1 phase of the eukaryotic cell cycle
- falls between end of cytokinesis and the start of DNA synthesis
3
Q
S phase
A
- synthesis
- period during a eukaryotic cell cycle in which DNA is synthesized
- DNA is replicated so there are two copies of each chromosome
4
Q
G2 phase
A
- Gap 2 phase of the eukaryotic cell cycle
- falls between the end of DNA synthesis and the beginning of mitosis
5
Q
M phase
A
- mitosis (prophase, prometaphase, metaphase, anaphase, telophase)
- cytokinesis
6
Q
How is the cell cycle regulated
A
- 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
7
Q
Describe importance of Gap phases
A
- 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
8
Q
cyclin
A
- 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
9
Q
Cdks
A
- 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
10
Q
Describe the Metaphase to Anaphase transition
A
- 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
11
Q
Describe APC at M phase
A
- 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
12
Q
What does M-Cdk phosphorylate?
A
- nuclear lamins
- proteins involved in DNA condensation
- proteins involved in making mitotic spindle
- activation of APC/C(degrades M cyclin)
13
Q
Why does M-Cdk phosphorylate nuclear lamins?
A
- causes breakdown of nuclear envelope
14
Q
Why does M-Cdk phosphorylate proteins involved in DNA condensation and proteins that make the mitotic spindle?
A
- condensins help pull chromosomes apart
- microtubule binding proteins
15
Q
S-Cdk
A
- 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
16
Q
How is the expression of cyclins and activity of Cdks regulated?
A
- transcription of cyclins
- Ubiquitylation by APC/C
- regulating Cdks directly
- protein binding inhibits activity of some Cdks
17
Q
Transcription of cyclins
A
- 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
18
Q
Ubiquitylation by APC/C
A
- 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
19
Q
Regulating Cdks directly
A
- phosphorylation: example MCdk
- protein binding inhibits activity of some Cdks, p21 inhibits G1/S and S Cdks
20
Q
APC/C
A
- 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
21
Q
Describe how M-Cdk is regulated by phosphorylation
A
- 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
22
Q
Cdk inhibitor proteins
A
- 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
23
Q
How are sister chromatids separated?
A
- separate at anaphase
- cohesins are proteins that hold sister chromatids together, degraded in anaphase
24
Q
What do mitogens do in cell cycle?
A
promote the production of cyclins that stimulate cell division (moving from G1 Phase to S Phase)
25
Describe how mitogens promote proliferation/cell division?
- 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
26
Describe how DNA damage can halt progression temporarily from G1 to S
- 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)
27
p53
- 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
28
Describe DNA damage checkpoint
- 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
29
What occurs when DNA damage cannot be repaired?
- apoptosis
30
Describe the trigger of Apoptosis
- Bax and Bak can trigger apoptosis by releasing cytochrome c from mitochondria
