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DEN 7101F - Human Structure and Function > Exam 2 10/11 Britton > Flashcards

Exam 2 10/11 Britton Flashcards

1
Q

What is the cell cycle

A

Set of 4 phases in which DNA/cellular components duplicate and divide into daughter cells

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2
Q

What are the phases of the eukaryotic cell cycle

A
  • G1
  • S phase
  • G2
  • M phase
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3
Q

Interphase is made up of:

A

G1, S phase, G2

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4
Q

G1 phase

A

cell grows and synthesizes all cellular components that are essential for DNA duplication

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5
Q

S phase

A

DNA synthesis replicates the genetic material
(each chromosome duplicated/2 sister chromatids)

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6
Q

G2 phase

A

Cell prepares for division in M phase

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7
Q

M phase

A

Mitosis/cytokinesis - generates 2 identical daughter cells

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8
Q

What are the cell cycle checkpoints?

Regulate cell cycle transition

A
  • G1 checkpoint
  • G2 checkpoint
  • M checkpoint
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9
Q

G1 checkpoint

A

determines whether conditions are favorable for cell division to proceed

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10
Q

G2 checkpoint

A

correct chromosome duplication is assessed

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11
Q

M checkpoint

A

attachment of each centromere to the spindle fibers is assessed, mitosis only proceeds if this is correct

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12
Q

At each cell cycle checkpoint, cell examines:

A

internal and external cues and decides whether or not to move forward with division

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13
Q

Cell enters next phase of division if:

A

Necessary conditions exist

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14
Q

Cell cycle is halted if:

A

Necessary conditions are not met

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15
Q

Normal cells transition through the cell cycle in a ____ way

A

Regulated

Cell division, growth, repair of genetic damage is regulated

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16
Q

Errors in checkpoints have _____

A

Catastrophic consequences - uncontrolled cell division or cell death

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17
Q

Regulation of the cell cycle involves what proteins/enzymes?

A
  • cyclins
  • cyclin dependent kinases (CDK)
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18
Q

____ are serine/threonine protein kinase enzymes that phosphorylate specific target proteins

A

CDKs

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19
Q

____ act as the signal for the cell to pass into the next phase of division

A

CDKs

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20
Q

CDKs are inactive in the absence of

A

Cyclins (cyclins bind to CDKs and activate them)

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21
Q

____ are regulatory proteins with no catalytic activity

A

Cyclins

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22
Q

True or false: Cyclins themselves have catalytic activity

A

False

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23
Q

After binding to CDKs, what eventually happens to cyclins?

A

Get degraded by cytoplasmic enzymes, deactivating the CDKs

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24
Q

Cyclin-CDK complexes are unique to:

A

Each cell cycle phase

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25
Q

Cyclin-CDK complexes activate:

A

Specific genes to drive cells through the cell cycle

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26
Q

Cyclin A can form a complex with which CDK(s)?

A

CDK 1 and CDK 2

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27
Q

Which phase of cell cycle is associated with CDK1 and Cyclin A/B complexes?

A

Mitosis

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28
Q

Cyclin E can form a complex with which CDK?

A

CDK 2

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29
Q

Which phase of cell cycle is associated with CDK2 and Cyclin A/E complexes?

A

Entry into S phase

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30
Q

Cyclin D can form complexes with which CDK?

A

CDK 4 and 6

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31
Q

Entry into G1 phase requires which cyclin/CDK complexes?

A

CDK4-cyclin D
CDK6-cyclin D

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32
Q

Cyclins and CDKs must undergo _____ during the cell cycle

A

constant cycle of synthesis and degradation

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33
Q

Before a cell can progress from one phase of the cell cycle to the next:

A

it must degrade the cyclin that characterizes that phase of the cell cycle

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34
Q

If cyclin is not degraded:

A

Cell cycle does not continue

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35
Q

Favorable conditions for replication

A
  • growth factor signals
  • DNA integrity
  • cell size
  • protein reserves assessed
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36
Q

What checkpoint is referred to as the restriction point?

A

G1

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37
Q

What happens at the restriction point?

A

Cell is committed to division and moves into the S phase

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38
Q

If conditions are not favorable during G1 checkpoint:

A

cell enters G0 resting state, await further signals when conditions improve

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39
Q

True or false: some cells remain in G0 for lifetime

A

True - neurons, skeletal muscle cells

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40
Q

Transition from G1 to S phase is ruled by: (2)

A
  • CDK4/6-cyclin D (G1 checkpoint)
  • CDK2-cyclin E (entry into S phase)
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41
Q

What is E2F

A

transcription factor important for cell growth

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42
Q

What happens when E2F is bound to retinoblastoma (Rb) protein?

A

Production of proteins necessary for G1/S transition is blocked

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43
Q

Rb

A

Retinoblastoma protein

tumor-suppressor protein/negative regulator of cell cycle

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44
Q

How does E2F get released from Rb?

A

CDK4/6-CyclinD phosphorylates Rb, releasing E2F

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45
Q

E2F induces ____ progression in association with ____

A

S-phase; CDK2-cyclin E

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46
Q

Ras protein is a

A

Proto-oncogene

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47
Q

Ras activates:

A

G1 checkpoint cyclins

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48
Q

What happens if Ras protein is mutated?

A
  • Becomes constantly active so will constantly activate G1 cyclins, leading to uncontrolled cell cycle into S phase
  • causes cancer
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49
Q

____ checkpoint prevents entry into M phase if certain conditions are not met

A

G2

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50
Q

What happens if DNA is not properly replicated/intact during S phase?

A
  • Cell cycle is paused at G2 checkpoint
  • cell will attempt to complete DNA replication or repair the damaged DNA
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51
Q

Forkhead box M1 protein

A

transcription factor that allows for transition to M phase

activates expression of FoxM1 target genes

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52
Q

In order for FoxM1 to become active, what needs to happen?

A

Needs to get phosphorylated by CDK2-cyclin A and CDK2-cyclin E

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53
Q

M checkpoint also known as

A

Spindle checkpoint

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54
Q

What are the mitotic CDK’s?

A

CDK1-cycin A, CDK1-cyclin B

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55
Q

G1/S phase CDKs are inhibited by

A

Mitotic CDKs

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56
Q

When mitotic CDKs are high during M phase, what happens?

A

factors that initiate DNA replication are inhibited

2nd DNA synthesis stopped til mitosis is complete/passes G1 checkpoint

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57
Q

Mitotic CDKs activate:

A

APC/C

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58
Q

APC/C function

A

allow chromatids to separate at anaphase and complete mitosis

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59
Q

___ decreases the possibility to aneuploidy

A

APC/C

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60
Q

Negative regulators of the cell cycle- function

A

Halt the cell cycle

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61
Q

Cyclins/CDKs are negatively regulated by

A

Cyclin-dependent kinase inhibitors (CKIs)

62
Q

Examples of negative regulators of the cell cycle

A
  • INK4 protein inhibitors of CDK4
  • CDK-interacting proteins
  • E3 ubiquitin enzyme
  • tumor suppressor proteins (p53, p21, Rb)
63
Q

Tumor suppressor proteins act primarily at the

A

G1 checkpoint

64
Q

True or false: tumor suppressor proteins are often mutated/damaged in cancer cells that replicated uncontrollably

A

True

65
Q

p53 function

A

halts cell cycle if damaged DNA is detected, recruits enzymes to repair the DNA

66
Q

Where is p53 found

A

In almost every cell

67
Q

p21 function

A

enforces the halt dictated by p53 by inhibiting the activity of CDK/cyclin complexes

68
Q

Rb binds to E2F transcription factor to:

A

block production of proteins needed for G1/S transition

69
Q

Many anti-cancer drugs act at the level of

A

Cell cycle signaling pathways

70
Q

1st and 2nd generation anticancer drugs inhibit

A

Range of CDKs

71
Q

3rd gen anticancer drugs

A

Specific inhibitors of CDK4 and CDK6 (G1 CDKs)

72
Q

Side effects of anticancer drugs

A
  • neutropenia
  • thrombocytopenia
73
Q

Even though we have many different cell types and organs:

A

All cells have the same genome

74
Q

What gives a cell its unique properties?

A

Different cells express different RNA transcripts and proteins due to gene regulation

75
Q

Central dogma

A

DNA to RNA to protein

76
Q

Genome is ____-specific

A

Species

77
Q

Exome

A
  • entire collection of RNA molecules
  • different in different tissues
78
Q

Proteome

A

Total collection of proteins in a cell

79
Q

_____ are always transcribed in all cell types

A

Housekeeping genes

80
Q

Examples of housekeeping genes

A

genes needed for DNA polymerases, metabolism proteins

81
Q

Specialized genes involve those which transcription is:

A

either on or off in certain cells

Hb only expressed in RBC

82
Q

Finely tuned genes can ____ in response to external signals

A

Change expression

83
Q

The set of genes expressed in a cell determines:

A

the set of RNAs and functional proteins it contains, giving it unique properties

84
Q

Many genes are regulated primarily at the level of:

A

transcription

85
Q

DNA normally exists as:

A

Chromatin/chromosomes

86
Q

How is chromatin formed?

A

When DNA wraps around histone/non-histone proteins

87
Q

Euchromatin

A

lightly packed, transcriptionally active

88
Q

Heterochromatin

A

Highly condensed, transcriptionally inactive

89
Q

What is the first stage of DNA compaction?

A

Nucleosome

90
Q

Methods of epigenetic modification

A
  • DNA methylation
  • Histone modifications
91
Q

What adds methyl group to DNA molecule?

A

DNA methyltransferase enzyme

92
Q

True or false: DNA methylation occurs anywhere on a DNA molecule

A

False - on CpG dinucleotide

93
Q

DNA methylation forms

A

5-methyl-cytosine

94
Q

DNA methylation acts as a signal/marker for:

A

other proteins that read the modification that then recruit other proteins who can modify the histones

95
Q

Histone proteins found in nucleosome

A

2 each of:
- H2A
- H2B
- H3
- H4

96
Q

Nucleosomes are further packed together by

A
  • histone N-terminal tails
  • histone H1 molecules
97
Q

Chromatin blocks access of

A

Transcription factors to potential DNA binding sites

98
Q

Changes in chromatin structure play a major role in:

A

regulating gene expression and DNA replication

99
Q

Mechanisms of changing chromatin structure

A
  • enzymatic modification of the histone N-terminal tails
  • ATP-driven chromatin remodeling complexes (ATP hydrolysis)
100
Q

Modifications of histone proteins include:

A
  • acetylation
  • methylation
  • phosphorylation
101
Q

Histone acetylation is done by

A

Histone acetyl transferase (HAT)

102
Q

Histone methylation is done by

A

Histone methyl transferase (HMT)

103
Q

Removal of acetyl groups of histones is done by

A

Histone deacetylase complex transferase (HDAC)

104
Q

Histone code

A

pattern of histone modifications; has specific meanings

105
Q

Methylation function

A

usually promotes heterochromatin formation to silence DNA transcription and gene expression

106
Q

ATP driven chromatin remodeling complex is thought to

A

Push on the DNA and loosen the attachment to the histone core, encourages transcription

107
Q

Gene regions include

A
  • coding region (introns and exons)
  • 5’ UTR
  • 3’ UTR
108
Q

Promoter

A

region upstream from a gene which is a binding site for transcription factors, RNA polymerase, etc

109
Q

Regulatory sequences

A

binding sites on DNA for various transcription factors

110
Q

Outcomes of transcription factors binding to DNA

A

Enhance, diminish, silence the transcription of a gene

111
Q

Where is regulatory sequence located relative to the associated gene?

A

At a distance

112
Q

Genetic switch

A

Transcription can be turned on and off in response to a variety of signals

113
Q

Components of a genetic switch

A
  • specific DNA sequences
  • proteins that bind to these DNA sequences
114
Q

Other names for transcription factors

A
  • DNA binding proteins
  • Gene regulatory proteins
115
Q

Specific transcription factors recognize:

A

specific DNA consensus sequences

116
Q

Transcription factors contain _____ that can read DNA sequences

A

Structural motifs

117
Q

Examples of transcription factors structural motifs

A
  • helix-turn-helix proteins
  • zinc finger proteins
  • leucine zipper proteins
118
Q

Transcription factors read ___ of DNA helix

A

outside of

119
Q

Positive control

transcription factors

A

When TFs bind to DNA and turn gene transcription on

120
Q

Negative control

transcription factors

A

When TFs bind to DNA and turn transcription off

121
Q

Negative control TFs are known as

A

Repressors/gene repressor proteins

122
Q

True or false: TFs can function as activators or repressors or both on different genes

A

True

123
Q

True or false: A single type of TF can regulate the expression of different genes

A

True

124
Q

TFs can form ____ and ____ proteins

A

Homomeric; heteromeric

125
Q

Combinatorial Gene Regulation

A

Different combinations of TFs can give rise to different cell/tissue types (ex. in development)

126
Q

____ are critical for development

A

Transcription factors

127
Q

Mutations in TF PAX9 results in

A

Partial/total anadontia

128
Q

Mutations in TF RUNX2 causes

A

Supernumerary teeth

129
Q

TATA box

A
  • Gene promoter
  • consensus sequence of TATAA/TAA/T
  • -30 upstream to gene transcription start site
130
Q

Before transcription can begin:

A

RNA polymerase II requires general transcription factors to assemble at the promoter

131
Q

Once TFs are recruited:

A
  • recruits RNA Pol II to promoter
  • position and help RNA Pol bind to promoter
132
Q

Initiation of transcription

A
  • DNA is pulled apart (helicase activity)
  • RNA Pol phosphorylated
133
Q

Post transcriptional control of gene expression methods

A
  • attenuation
  • RNA processing
  • RNA transport
134
Q

Attenuation

A
  • premature termination of an RNA molecule while being transcribed
  • growing RNA chain creates a structure that interacts with RNA Pol to cause it to stop transcription
135
Q

Pre-mRNA

A

primary mRNA transcripts in the nucleus

136
Q

RNA transcript processing involves

A
  • 5’ capping
  • 3’ polyadenylation
  • splicing
137
Q

When does RNA processing occur

A

As soon as transcript is being made

138
Q

Exon-intron junctions contain

A

Consensus sequences (where splicing happens)

139
Q

GU-AG rule

A

mRNA splicing - GU at 5’, AG at 3’

140
Q

Spliceosome

A

complex of small nuclear RNA (snRNA) and ribonucleoproteins

141
Q

Lariat

A

Loop structure resulting from cut 5’ end of intron that links to adenine

142
Q

Intron is removed as a shape of a

A

Lariat

143
Q

Splicing makes genes more

A

Modular - allows new combinations of exons to be created

144
Q

Alternative splicing gives rise to

A

Different proteins rising from single mRNA transcript

145
Q

Example of a gene that undergoes alternative splicing

A
  • Tropomyosin gene
  • amelogenin gene (exon 4 inclusion detrimental to enamel matrix formation)
146
Q

Alternative exon splicing can cause disease such as in:

A

abnormal processing of the beta globin transcript in beta thalassemia

mutations can give rise to abnormal exon splicing

147
Q

Alternative splicing can be regulated by

A

Activator and repressor proteins

148
Q

Where are RNAs transported from/to

A

From nucleus to cytoplasm

149
Q

Where is mRNA processed

A

In nucleus before leaving for cytoplasm

150
Q

RNA exits via

A

Nuclear pore complexes that cover the nuclear membrane

151
Q

The amelogenin gene is composed of ____ exons

A

7
(inclusion of 4 deleterious to enamel production)

DEN 7101F - Human Structure and Function (23 decks)

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