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Biochem 524 > Chapter 17 - The Cell Cycle > Flashcards

Chapter 17 - The Cell Cycle Flashcards

1
Q

How long does M-phase take in mammalian cells?

A

Less than an hour

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2
Q

Prophase

A
  1. The two DNA molecules are gradually disentangled
  2. They are condensed into pairs of compact rods called sister chromatids
  3. Nuclear membrane disassembles
  4. Sister chromatids are attached to spindles
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3
Q

Metaphase

A

Spindles move sister chromatids to center of the cell and are aligned

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4
Q

Anaphase

A

Sister chromatids are pulled apart by spindles to opposite sides of the cell

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5
Q

Telophase

A
  1. Spindles disassemble

2. Segregated chromosomes are packaged into separate nuclei

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6
Q

Cytokinesis

A

Cell cleaves into two cells so that each inherits one of the nuclei that holds an entire copy of the full set of chromosomes

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7
Q

Eukaryotic cell cycle

A
  1. G1
  2. S
  3. G2
  4. M
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8
Q

Interphase

A

Collectively all stages before M-phase: G1, S and G2

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9
Q

Average human cell interphase and M-phase time

A
  1. 23-24hours for interphase

2. 1 hour for M-phase

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10
Q

Point at which the cell commits to continue the cell cycle

A

Restriction point, also known as start in yeast cells

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11
Q

Model organisms for fundamental genes proteins and features of cell cycle.

A
  1. Budding yeast (Saccharomyces cerevisiae)

2. Fission yeast (Schizosaccharomyces pombe)

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12
Q

Model organism used for biochemical dissection of cell-cycle control mechanisms

A

Frog - Xenopus laevis

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13
Q

Mode organism for genetic analysis of mechanisms underlying the control and coordination of cell growth and division in multicellular organisms

A

Fruit fly: Drosophila melanogaster

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14
Q

How can we tell what stage of the cell cycle has been reached?

A
  1. Looking through microscope can reveal
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15
Q

What are the three transitions of the cell cycle?

A
  1. Start transition (G1 entering S)
  2. G2/M transition
  3. Metaphase-to-anaphase transition
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16
Q

What does start transition control look for before transition?

A

Is environment favorable?

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17
Q

What does G2/M transition control look for before transition?

A
  1. Is environment favorable?

2. Is all DNA replicated?

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18
Q

What does meta-ana transition control look for before transition?

A
  1. Are all chromosomes attached to spindle?
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19
Q

Central components of cell cycle

A

Cyclin-dependent kinases (Cdks)

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20
Q

G1/S-cyclins

A

Activate Cdks in late G1 and thereby help trigger progression through Start, resulting in a commitment to a cell-cycle entry

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21
Q

When do G1/S-cyclins levels fall?

A

S-phase

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22
Q

S-cyclins

A
  1. Bind Cdks soon after progression through Start
  2. help stimulate chromosome duplication
  3. Some of these cyclins also contribute to the control of certain early mitotic events
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23
Q

S-cyclin levels remain elevated until…

A

Mitosis

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24
Q

M-cyclin

A

Activates Cdks that stimulate entry into mitosis at G2/M transition.

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25
Q

M-cyclin levels fall…

A

in mid-mitosis

26
Q

G1-cyclins

A

Helps govern the activities of the G1/S-cyclins which control progression through start in late G1

27
Q

G1-Cdk vertebrates:

  1. Cycling
  2. Partner
A
  1. Cyclin D (three kind D1…D3)

2. Cdk4, Cdk6

28
Q

G1/S-Cdk vertebrates:

  1. Cycling
  2. Partner
A
  1. Cyclin E

2. Cdk2

29
Q

S-Cdk vertebrates:

  1. Cycling
  2. Partner
A
  1. Cyclin A

2. Cdk2, Cdk1

30
Q

M-Cdk vertebrates:

  1. Cycling
  2. Partner
A
  1. Cyclin B

2. Cdk 1

31
Q

What Cdk binds to cyclins in budding yeast?

A

Cdk1

32
Q

What happens to active site of Cdk in absence of cyclin?

A

The active site is obscured by a protein loop inside protein

33
Q

What fully activates cyclin-Cdk complex?

A

Cdk-activating kinase (CAK) by phosphorylating amino acid near entrance of Cdk active site

34
Q

What inhibits cyclin-Cdk complex by phosphorylation?

A
  1. Wee1

2. By phosphorylation at a pair of amino acids in the roof of the kinase active site.

35
Q

What reactivates cyclin-Cdk complex by de phosphorylation?

A

Cdc25 phosphatase

36
Q

What Cdk is the phosphorylation inhibition primarily used for?

A

M-Cdks

37
Q

What protein inhibits complex by binding itself to it? How?

A
  1. Cdk inhibitor proteins (CKIs)

2. binding stimulates large rearrangement of Cdk active site rendering it inactive

38
Q

Cells primarily use CKIs to help…

A

govern the activities of G1/S- and S-Cdks early in the cell cycle.

39
Q

What triggers metaphase-to-anaphase transition?

A
  1. Regulated proteolysis

2. Anaphas-promoting complex or cyclosome (APC/C) polyubiquilate specific target proteins

40
Q

What two major proteins do APC catalyzes the ubiquitylation?

A
  1. Securin

2. S-cyclins and M-cyclins

41
Q

How long does the average mammalian S-phase take?

A

10-12hrs

42
Q

Role of Securin

A

Protects the protein linkages that hold sister-chromatid pairs together in early mitosis

43
Q

Destruction of Securin causes

A

In metaphase, activates a protease that separates the sisters and unleashes anaphase

44
Q

Destruction of S-cyclins and M cyclins

A

Inactivates most Cdks in cell

45
Q

APC activity during cell cycle

A
  1. Active in G1 to provide a stable period of Cdk inactivity

2. When G1/S-Cdk is activates in late G1, APC is turned off allowing cyclin accumulation

46
Q

SCF

A
  1. Ubiquitylates certain CKI proteins in late G1

2. Responsible for destruction of G1/S-cyclins in early S-phase

47
Q

How is APC regulated?

A
  1. Changes in association with an activating subunit (Cdc20 in mid-mitosis and Cdh1 in late mitosis through early G1)
  2. These subunits help recognize target proteins.
48
Q

How is SCF activity regulated?

A
  1. SCF activity remains constant

2. But phosphorylation states of target proteins determines whether they get recognized or not, by F-box subunit of SCF.

49
Q

Cdk-activating kinase (CAK)

A

Phosphorylates an activating site in Cdks

50
Q

Wee1 kinase

A

Phosphorylates inhibitory sites in Cdks - primarily involved in suppressing Cdk1 activity before mitosis

51
Q

Cdc25 phosphatase

A
  1. Removes inhibitory phosphates from Cdks
  2. Three family members Cdc23A, B and C
  3. Primarily involved in controlling Cdk1 activation at the onset of mitosis
52
Q

Sic1

A
  1. Budding yeast
  2. Suppresses Cdk1 activity in G1
  3. Phosphorylation by Cdk1 at the end of G1 triggers it’s destruction
53
Q

p27

A
  1. Mammals
  2. Suppresses G1/S-Cdk and S-Cdk activities in G1.
  3. Helps cells withdraw from cell cycle when they terminally differentiate
  4. Phosphorylation by Cdk2 triggers it’s ubiquitylation by SCF
54
Q

p21

A
  1. Mammals

2. Suppresses G1/S-Cdk and S-Cdk activities following DNA damage

55
Q

p16

A
  1. Mammals
  2. Suppresses G1-Cdk activity in G1
  3. Frequently inactivated in cancer
56
Q

Cdc20

A
  1. APC-activating subunit in all cells
  2. Triggers initial activation of APC at metaphase-to-anaphase transition
  3. Stimulated by M-Cdk activity
57
Q

Cdh1

A
  1. APC-activating subunit
  2. Maintains APC activity after anaphase and throughout G1
  3. Inhibited by Cdk activity
58
Q

First step to ensure chromosomes replicate once

A
  1. Occurs in late mitosis and early G1
  2. When a pair of inactive helicases is loaded onto the replication origin forming a large complex called the prereplicative complex or preRC.
  3. Step sometimes called licensing of replication origins because initiation of DNA synthesis is only permitted at origins containing preRC
59
Q

Second step cell does to ensure chromosome duplication only occurs once.

A
  1. Occurs in S-phase
  2. DNA helicases are activated, resulting in DNA unwinding and the initiation of DNA synthesis.
  3. Once replication origin is fired, the helicases move out from the origin with the replacement form.
  4. Origin cannot be reused until a new preRC is assembled there at the the end of mitosis
60
Q

How is cell-cycle system reset to allow replication in the next cycle?

A
  1. End of mitosis, APC activation leads to inactivation of Cdks and the destruction of geminin
  2. ORC and Cdc6 are dephosphorylated and Cdt1 is activated
  3. allowing preRC assembly to prepare cell for next S phase
61
Q

Cohesins

A

Hold sister chromatids together

Biochem 524 (6 decks)

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