Phys Concepts 1.17 Flashcards

1
Q

What is the cell cycle?

A

The orderly sequence of events by which a cellduplicates its contents and divides in two

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2
Q

The cell cycle is driven by specific molecular signals present in the __

A

cytoplasm

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3
Q

The cell cycle consists of 2 phases, what are they?

A
  • mitotic (M) phase (mitosis and cytokinesis)
  • interphase (cell growth and copying of chromosomes in preparation for cell division)
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4
Q

Interphase is about _% of the cell cycle

A

90

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5
Q

Interphase can be divided in subphases, what are they?

A
  • G1 phase: first gap
  • S phase: synthesis
  • G2 phase: second gap
  • G0 phase: resting phase, postmitotic quiescent
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6
Q

What is interphase?

A

cell growth and copying of chromosomes in preparation for cell division

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7
Q

What is the grey? What is the peach?

A

grey: interphase
peach: mitosis

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8
Q

What is G1?

A

first gap phase

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9
Q

What is the cell preparing for in G1?

A

entering DNA synthesis phase

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10
Q

T/F: Cell is metabolically active in G1.

A

True

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11
Q

What does G1 require? What synthesis is occuring?

A
  • Requires nutrients & growth factors
  • RNA, protein, lipid and carbohydrate synthesis occurs
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12
Q

T/F: No organelles are duplicated in G1

A

False, many are

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13
Q

How long is G1?

A

variable (6-24 hours)
- short in embryonic and cancer cells
- rapid or non-existent in rapidly dividing cells

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14
Q

What phase is DNA and chromosomal protein synthesis occuring?

A

S

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15
Q

What is the duration of S phase?

A

approx. 7-8 hours in a typical mammalian cell w/ a 16 hour cycle

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16
Q

What is the cell committed to in S phase?

A

cell division

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17
Q

T/F: growth factors are needed in S phase

A

False

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18
Q

What phase does DNA replication occur?

A

S phase

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19
Q

What is G2 phase?

A

second growth phase

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20
Q

What occurs at G2 phase?

A

enzyme, protein, and ATP synthesis

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21
Q

What is the duration of G2?

A

lasts approximately 3 hours in a typical mammalian cell with a 16-hour cycle

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22
Q

What is M phase?

A

mitotic phase

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23
Q

What does the cell undergo during M phase?

A

mitosis and cytokinesis

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24
Q

What is the duration of the M phase?

A

1-2 hours

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25
Q

M phase is about _% of the cell cycle

A

10

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26
Q

What state is the cell in in G0 phase?

A

state of withdrawal from cell cycle

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27
Q

Is the cell dividing or preparing to divide in G0?

A

neither

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28
Q

What is the cell doing during G0?

A

Instead, the cell is “doing its job” - performing it’s function within the tissue

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29
Q

What are examples of cells in G0?

A

hepatocytes, neurons

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30
Q

What type of cell is G0 common in?

A

differentiated cells

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31
Q

In order to progress through the cell cycle, a variety of __ must be turned on.

A

signals

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32
Q

What happens if the environment is not favourable or there are errors in DNA?

A

the cell cycle is “paused” at several main check points (aka “transitions”)

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33
Q

What are checkpoints of the cell based on?

A

series of biochemical switched to initiate a specific cell-cycle events

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34
Q

What is the cell cycle control system?

A

Checkpoints, biochemical switches that decide whether the cell cycle continues

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35
Q

what are features of the biochemical switched?

A
  1. Generally binary (on/off) to launch an event in a complete & irreversible fashion
  2. Robust & reliable
  3. Adaptable & modified to suit specific cell types
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36
Q

How are biochemical switched robust & reliable?

A

Contains back up mechanisms to ensure efficacy under variable conditions & if some components fail

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37
Q

How are biochemical switched adaptable and modified to suit specific cell types?

A

Responds to specific intracellular or extracellular signals
Cyclin dependent kinases (Cdks)

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38
Q

What are checkpoints (transitions)?

A

Points in the eukaryotic cell division cycle where progress through the cycle can be halted until conditions are suitable for the cell to proceed to the next stage

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39
Q

What are checkpoints regulated by?

A
  • Factors within the cell, mostly controlled by the “health” or “state of preparation” of the cell
  • Factors from outside the cell – i.e. messages from other cells within the same tissue or distant cells
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40
Q

Where are the 3 major regulatory transitions?

A
  1. Start Transition (aka G1/S)
  2. G2/M transition
  3. Metaphase-to-anaphase transition (aka M-to-A)
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41
Q

For most cells, the G1/S seems to be the __-__ and __ step of the cell cycle

A

rate-limiting; committing

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42
Q

Which phase is the rate-limiting and committing step of the cell cycle?

A

G1/S

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43
Q

__ __ MUST be present for a cell to pass through the following checkpoints

A

specific signals

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44
Q

If cell detects problem inside or outside the cell, what happens?

A

it will block progression beyond the checkpoint

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45
Q

If extracellular conditions are not appropriate for cell proliferation, what happens?

A

central control system blocks progression through the start transition

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46
Q

If there is a problem with completion of DNA replication, what happens?

A

cell will be held at G2/M checkpoint

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47
Q

If all the chromosomes are not attached to the spindle, what happens?

A

cell will be held at M phase (metaphase to anaphase)

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48
Q

What are the keys to the cell cycle control system?

A

cyclin-dependent kinases (Cdks)

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49
Q

What are Cdks responsible for?

A

cyclical changes in phosphorylation of intracellular proteins that initiate/regulate the major events of the cell cycle

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50
Q

What are Cdks controlled by?

A

cyclins

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51
Q

What do cyclical changes in cyclin protein levels result in?

A

cyclic assembly and activation of cyclin–Cdk complexes at specific stages of the cell cycle

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52
Q

What is needed to progess through a checkpoint? What is the exception of this?

A
  • Correct & functional cyclin-cdk complexes
  • Exception: M-to-A checkpoint is a little different
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53
Q

What are the 4 different class of cyclins?

A
  1. G1 cyclins: cyclin D
  2. G1/S cyclins: cyclin E
  3. S-cyclins: Cyclin A
  4. M cyclins: Cyclin B
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54
Q

What do G1 cyclins (cyclin D) form complex with?

A

Cdk4 or Cdk 6

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55
Q

What is G1 cyclin (cyclin D) used for?

A

Involved in G1 phase of cell cycle, needed for initiation of transcription of G1/S cyclins to help promote passage through start transition

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56
Q

What do G1/S cyclins (Cyclin E) form complex with?

A

Cdk2

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57
Q

What does G1/S cyclins (cyclin E) do?

A
  • Bind Cdk’s at the end of G1 & help trigger progression through start transition
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58
Q

When do levels of cyclin E decrease?

A

in S phase

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59
Q

What does S-cyclin (cyclin A) form a complex with?

A

Cdk1 and Cdk2

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60
Q

What does cyclin A do?

A

Bind Cdks after progression through start transition & helps stimulate chromosome duplication during S phase

contributes to control of some early mitotic events

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61
Q

What does Cyclin B form a complex with?

A

Cdk1

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62
Q

What does cyclin B do?

A

Bind CdKs to stimulate entry into mitosis at the G2/M transition

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63
Q

When do levels of cyclin B decrease?

A

mid-mitosis

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64
Q

How do cyclin-Cdk complexes work?

A

cyclins function by activating the Cdk

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65
Q

How does cyclin protein activate Cdk?

A

directs it to a specific target protein

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66
Q

T/F: A cyclin-CdK complex can induce different effects at different times in the cell cycle

A

True

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67
Q

Why can cyclin-Cdk complex induce different effects at different times in the cell cycle?

A

Since accessibility of CdK substrates change during the cell cycle

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68
Q

Proteins that function in mitosis mat only become available for phosphorylation in what stage?

A

G2

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69
Q

How does progression through the metaphase-to-anaphase checkpoint occur?

A

via regulated proteolysis

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70
Q

What is regulated proteolysis?

A

regulated break down of proteins

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71
Q

What is APC/C stand for?

A

anaphase promoting complex

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72
Q

What is APC/C a family of?

A

ubiquitin ligase

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73
Q

What is APC/C used for?

A

Used to stimulate proteolytic destruction of specific regulatory proteins
- APC/C polyubiquitinates specific target proteins for destruction in proteasomes

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74
Q

What are target proteins of APC/C?

A

securin, M-cyclins, S-cyclins

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75
Q

__ __ bind to specific receptors to stimulate cellular growth and proliferation

A

growth factors

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76
Q

What do growth factors turn on in G1 phase?

A

early response genes and delayed response genes

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77
Q

What do early response genes code for?

A

transcription factors - induce transcription of delayed response genes

78
Q

What do delayed response genes code for?

A

usually Cdks, cyclins, or other proteins needed for cell division

79
Q

In G1, in response to binding of growth factor, what happens?

A

Cyclin D and then E are transcribed and translated and form complexes with their Cdk’s

80
Q

What is the complex of cyclin D and Cdk4 & Cdk6 called?

A

G1-Cdk complex

81
Q

What is the complex of cyclin E and Cdk2 called?

A

G1/S-Cdk complex

82
Q

What allows progression through the G1/S checkpoint?

A

active G1-Cdk and G1/S-Cdk

83
Q

At the G1/S checkpoint, Active G1-cdk (and G1/S-cdk) complex will target a protein called? And do what to it?

A

RB and phosphorylate it

84
Q

How does RB function?

A

transcription co-repressor

85
Q

Hyperphosphorylation of RB will __ RB

A

inactivate

86
Q

What does inactive RB release? What does this cause?

A

transcription factor E2F, allowing transcription to proceed

87
Q

Transcription of cyclin E => G1/S-cdk complex form, does what?

A

promotes passage through the start transition

88
Q

In early S phase, cyclin D (G1-cdk complex) and E (G1/S-cdk complex) are targeted for?

A

destruction

89
Q

What promotes progression through S phase?

A

desruction of cyclin D (G1-cdk complex) and E (G1/S-cdk complex)

90
Q

Active S-cdk complex allows?

A

progression through the S phase of the cell cycle

91
Q

S-Cdk complex levels are still high in?

A

G2

92
Q

M-cyclin levels begin to rise in?

A

G2

93
Q

M-cyclin levels begin to rise in G2 forming?

A

M-Cdk complex

94
Q

What is the M-Cdk complex needed for?

A

to pass through G2/M checkpoint

95
Q

At the end of G2, what is destroyed?

A

S-cyclins

96
Q

How are S-cyclins destroyed?

A

Targeted for proteolysis by APC/C

97
Q

Why do we need to be able to control activity of M-cyclins?

A

so that mitosis doesn’t start too soon

98
Q

Once the M-Cdk complex is assembled, what happens to it immediately?

A

it is inhibited vis phosphorylation

99
Q

When the cell is ready for mitosis to begin, the M-Cdk complex is __-__.

A

de-phosphorylated

100
Q

When can the cell progress through G2/M checkpoint & mitosis begins?

A

once M-Cdk is de-phorphorylated

101
Q

M-cdk complex is needed for?

A

activation of various proteins needed in mitosis

102
Q

Where is the final checkpoint?

A

metaphase-to-anaphase (M-to-A) checkpoint

103
Q

APC/C complex targets a protein called securin by ubiquitylation for?

A

destruction by a proteosome

104
Q

What is securin?

A

an inhibitory protein that protects protein linkages that hold sister-chromatid pairs together in early mitosis

104
Q

What does destruction of securin activate?

A

protease that separates the sister chromatids allowing progression to anaphase

105
Q

At the end of mitosis, M-cyclins are targeted for?

A

destruction by APC/C

105
Q

What does destroying M-cyclins do?

A

inactivates most Cdks in cell

106
Q

When many Cdks in the cell are inactivated at the end of mitosis, what happens?

A

many proteins phosphorylated by Cdks from S phase to early mitosis are dephosphorylated by various phosphatases in the anaphase cell

107
Q

What is required for the completion of M phase, including the telophase and then cytokinesis ?

A

Dephosphorylation of Cdk targets

108
Q

In unfavourable conditions, what happens to the cell cycle?

A

can be paused at any of the main checkpoints

109
Q

When is progression through G1 delayed?

A
  • DNA is damaged by radiation, chemicals, or errors
  • Absence of nutrients or growth factors
  • Abnormal cell size
110
Q

When is entry into M prevented?

A
  • DNA replication is not complete
  • Presence of DNA damage
  • Abnormal cell size
111
Q

When is progression through M-to-A prevented?

A

Chromosomes are not properly attached to mitotic spindle

112
Q

What are two important molecular mechanisms in unfavourable conditions?

A
  • Cdk inhibitory proteins (CKIs)
  • Proteins coded by tumour suppressor genes
113
Q

What does binding of Cdk inhibitory proteins do?

A
  • Inactivates cyclin-Cdk complex
  • stimulate rearrangement in structure of Cdk active site
114
Q

Who are CKI’s primarily used by? What for?

A

used by cells to govern the activities of G1/S- and S-Cdks early in cell cycle

115
Q

What are 3 important CKIs?

A

p16, p21, p27

116
Q

What does p16 inhibit?

A

CyclinD-cdk4 & CyclinD-cdk5 (G1-cdk complex)

117
Q

What does p21 inhibit?

A

CyclinE-cdk2 (G1/S-cdk complex)
CyclinA-cdk2 & CyclinA-cdk1 (S-cdk complex)
Cyclin B-cdk1 (M-cdk complex)

118
Q

What does p27 inhibit?

A

CyclinA-cdk2 & CyclinA-cdk1 (S-cdk complex)
CyclinE-cdk2 (G1/S-cdk complex)
Cyclin B-cdk1 (M-cdk complex

119
Q

What are 2 key tumour suppressor genes?

A

p53, RB

120
Q

What do p53’s do?

A
  • Recognizes and binds damaged DNA
121
Q

Why do unstressed cells have lower levels of p53?

A

since it will be bound by a protein called Mdm2 and be degraded

122
Q

What does RB do?

A
  • recognize damaged DNA
123
Q

What form is RB found in?

A

active form

124
Q

In the presence of DNA damage, __ will be __, releasing __

A

p53; phosphorylated; Mdm2

125
Q

T/F: In the presence of DNA damage, p53 is degraded

A

False

126
Q

Active p53 binds __ and promotes the transcription of __

A

DNA; p21

127
Q

An inactive G1/S-cdk complex will pause the cell cycle at the ____ transition

A

start

128
Q

In the presence of a growth suppressor signal or DNA damage __ is transcribed.

A

p16

129
Q

What does p16 inhibit? What was this needed for?

A

G1-Cdk complex which was needed to inactivated RB

130
Q

Since p16 was transcriped, RB remains activated and bound to __.

A

E2F

131
Q

What does RB bound to E2F cause?

A
  • no transcription of G1/S-cyclins or S-cyclins
  • cell cycle is paused at start transition
132
Q

The cell cycle progression can also be inhibited due to contact with?

A
  • other cells - density-dependent inhibition
  • basement membrane or other matrix component - anchorage dependence
133
Q

What is contact inhibition regulated by?

A

cadherins and beta-catenin

134
Q

What do survival signals promote?

A

the cell cycle and prevent apoptosis

135
Q

What pathway is used by survival signals to promote cell cycle and prevent apoptosis?

A

PI3K-Akt-mTOR C pathway

136
Q

How does Akt in the PI3K-Akt-mTOR C pathway promote cell cycle progression?

A
  • Akt activates/increases:
    Cyclin A –> activation of CDK-1
    Cyclin D –> activation of CDK-4/6
    Akt decreases/inactivates: p21 and p27
137
Q

What is the template for DNA duplication?

A

The DNA double helix acts as a template for its own duplication

138
Q

What will each daughter cell inherit?

A
  • DNA double helix containing 1 original strand and 1 new strand
139
Q

What are the 4 steps of DNA replication?

A
  • strand separation
  • primer creation
  • DNA replication
  • primer removal
140
Q

What bonds help contribute to stability of DNA?

A
  • H-bonds b/w complementary base-pairs
  • Phosphodiester bond within sugar-phosphate backbone
  • Hydrophobic effect due to base-stacking
141
Q

in step 1 (strand separation), what is needed in order for DNA synthesis to begin?

A

DNA double helix must open up

142
Q

What are two proteins are used to open up the double helix?

A
  • DNA helicase
  • single stranded binding proteins
143
Q

What does DNA helicase do?

A

unwinds double helix - breaks H bonds

144
Q

What do single stranded binding proteins do?

A

Bind tightly and cooperatively to stabilize the single strand conformation

145
Q

In step 1 (strand separation), what does opening the double helix create?

A

replication fork

146
Q

What is used at the replication fork to synthesize both new daughter strands of DNA?

A

DNA polymerase

147
Q

What are limitations of DNA polymerase?

A
  • can only add nucleotides
  • only works in 5’ to 3’ direction
148
Q

Why is a primer built in stage 2?

A

DNA polymerase can only add nucleotides to an existing strand of DNA (can only elongate a strand of nucleic acid)

149
Q

What does the primer in stage two serve as?

A

base-paired chain on which to add new nucleotides

150
Q

What is the primary made of in step 2?

A

RNA

151
Q

What makes the primer in stage 2?

A

DNA primase

152
Q

Step 2: Since DNA can only be synthesized in the 5’ to 3’ direction, the replication fork has an __ __

A

asymmetric structure

153
Q

What is the difference between the leading strand and lagging strand in step 2?

A
  • Leading strand: synthesized continuously
  • Lagging strand: synthesized discontinuously. The direction of nucleotide polymerization is opposite to the overall direction of DNA chain growth
154
Q

How many primers are required to start replication on the leading strand?

A

only one

155
Q

How many primers are needed to start replication on the lagging strand?

A

one for each Okazaki fragment

156
Q

What step is when DNA polymerase adds nucleotides in the 5’ to 3’ direction?

A

step 3 - DNA replication

157
Q

In step 4, how are RNA primers removed and replaced with what?

A

by DNA repair system replaced w/ DNA

158
Q

What does DNA ligase do in step 4?

A

joins 3’ end of new DNA fragment w/ 5’ end of previous fragment

159
Q

How does supercoiling occur?

A

As the replication fork moves along the double-strand DNA, anything in front of the replication fork will become overwound forming supercoils.

160
Q

What does DNA topoisomerase do? What does this allow?

A
  • relieves the super-helical tension by breaking the phosphodiester bond
  • allows the two sections of the DNA helix to rotate freely & relieve tension
  • phosphodiester bond will re-form as DNA topoisomerase leaves
161
Q

Why are histones needed in DNA replication?

A

so newly replicated DNA can be packaged into nucelosomes

162
Q

When does histone synthesis occur?

A

during the S phase of the cell cycle

163
Q

What do histone chaperones assist?

A

formation of assembly of histone octomer & nucleosomes

164
Q

Only about _ mistake occurs for every 10^10 nucleotides during DNA replication

A

1

165
Q

What are the DNA proofreading mechanisms?

A
  • DNA polymerase activity
  • exonucleolytic proofreading
  • strand-directed mismatch repair system
166
Q

When does DNA polymerase proofreading activity take place?

A

just prior to a new nucleotide being covalently added to the growing daughter chain

167
Q

How does the DNA polymerase proofreading activity work?

A
  • Correct nucleotide has higher affinity for the DNA polymerase than an incorrect nucleotide
  • So, energetically, incorrectly paired nucleotides are less favourable and therefore more likely to diffuse away before the DNA polymerase can add them by mistake
168
Q

When does exonucleolytic proofreading occur?

A

immediately after an incorrect nucleotide has been covalently added to the growing daughter chain

169
Q

How does exonucleolytic proofreading work?

A
  • An incorrectly added nucleotide will not provide an effective 3’-OH end for DNA polymerase to add on the next nucleotide
  • Separate catalytic site on DNA polymerase will initiate DNA polymerase to move in the 3’ –> 5’ direction, cliping off any unpaired or mispaired residues
  • Catalytic site: 3’-to-5’ proofreading exonuclease
170
Q

What deals with the problem of the lagging strand ending up with a shorter DNA fragment on the daughter strand once the RNA primer has been removed?

A

telomeres

171
Q

What are telomeres?

A
  • Eukaryotes have specialized nucleotide sequences at the end of their chromosomes
  • in humans: many repeats of GGGTTA
172
Q

What are telomere DNA sequences recognized by?

A

telomerase

173
Q

What does telomerase do?

A

replenish telomere sequences each time a cell divides

174
Q

What cells have full telomerase activity?

A

stem cells

175
Q

What cells have low/minimal telomerase activity? Why?

A
  • most cells
  • telomeres gradually shorten until a descendant cell inherits chromosome that lack telomere function
  • Initiates a response causing them to withdraw permanently from the cell cycle and cease dividing - Called replicative cell senescence
176
Q

What is replicative cell senescence?

A

when a cell will cease dividing due to low telomerase activity and telomere function is lacking

177
Q

What does telomerase recognize?

A

the tip of an existing telomere DNA repeat on the parent strand and elongate it in the 5’ to 3’ direction

178
Q

What does telomerase use as a template?

A

a intrinsic RNA template

179
Q

After telomerase is done its job, what happens?

A

DNA polymerase can complete the replication

180
Q

What are the 5 phases of mitosis?

A

Prophase
Prometaphase
Metaphase
Anaphase
Telophase & cytokinesis

181
Q

What is the end-product of mitosis?

A

two identical daughter cells

182
Q

What occurs during prophase?

A
  • Chromosomes condense
  • Since chromosomes have been replicated they consist of 2, closely-associated sister chromatid
  • Mitotic spindles assemble between the two centrosomes
  • Centrosomes have been replicated and are being moved apart
183
Q

What is a centrosome? What does it consist of?

A
  • protein organelle
  • Consists of a pair of centrioles surrounded by a cloud or amorphous material (called pericentriolar matrix)
184
Q

T/F: Centrosomes undergo replication during the cell cycle in preparation for mitosis

A

True

185
Q

What happens during prometaphase?

A
  • Nuclear envelope breaks down
  • Chromosomes attach to spindle microtubules via a protein called a kinetochore
186
Q

What happens during metaphase?

A
  • Chromosomes align at the equator of the cell (halfway between the spindle poles)
  • Kinetochore microtubules attach sister chromatics to opposites poles of the spindle
187
Q

What happens during anaphase?

A
  • Chromatids synchronously separate forming two daughter chromosomes
  • Kinetochore microtubules get shorter while spindle pole moves apart
  • Both these processes contribute to separation of chromosomes
188
Q

What happens during telophase?

A
  • Daughter chromosomes arrive at poles of spindle
  • Chromosomes decondense and a new nuclear envelope reassembles around each set
189
Q

What happens during cytokinesis?

A

Cytoplasm divides in two forming two daughter cells

190
Q

How would you describe the number of chromosomes in each of the following stages of the cell cycle: (n, 2n, 4n, other)
A) G1 of the cell cycle
B) Prophase
C) After cytokinesis

A

A) 2n
B) 2n
C) 2n