Exam 2 10/11 Britton Flashcards
(151 cards)
1
Q
What is the cell cycle
A
Set of 4 phases in which DNA/cellular components duplicate and divide into daughter cells
2
Q
What are the phases of the eukaryotic cell cycle
A
- G1
- S phase
- G2
- M phase
3
Q
Interphase is made up of:
A
G1, S phase, G2
4
Q
G1 phase
A
cell grows and synthesizes all cellular components that are essential for DNA duplication
5
Q
S phase
A
DNA synthesis replicates the genetic material
(each chromosome duplicated/2 sister chromatids)
6
Q
G2 phase
A
Cell prepares for division in M phase
7
Q
M phase
A
Mitosis/cytokinesis - generates 2 identical daughter cells
8
Q
What are the cell cycle checkpoints?
Regulate cell cycle transition
A
- G1 checkpoint
- G2 checkpoint
- M checkpoint
9
Q
G1 checkpoint
A
determines whether conditions are favorable for cell division to proceed
10
Q
G2 checkpoint
A
correct chromosome duplication is assessed
11
Q
M checkpoint
A
attachment of each centromere to the spindle fibers is assessed, mitosis only proceeds if this is correct
12
Q
At each cell cycle checkpoint, cell examines:
A
internal and external cues and decides whether or not to move forward with division
13
Q
Cell enters next phase of division if:
A
Necessary conditions exist
14
Q
Cell cycle is halted if:
A
Necessary conditions are not met
15
Q
Normal cells transition through the cell cycle in a ____ way
A
Regulated
Cell division, growth, repair of genetic damage is regulated
16
Q
Errors in checkpoints have _____
A
Catastrophic consequences - uncontrolled cell division or cell death
17
Q
Regulation of the cell cycle involves what proteins/enzymes?
A
- cyclins
- cyclin dependent kinases (CDK)
18
Q
____ are serine/threonine protein kinase enzymes that phosphorylate specific target proteins
A
CDKs
19
Q
____ act as the signal for the cell to pass into the next phase of division
A
CDKs
20
Q
CDKs are inactive in the absence of
A
Cyclins (cyclins bind to CDKs and activate them)
21
Q
____ are regulatory proteins with no catalytic activity
A
Cyclins
22
Q
True or false: Cyclins themselves have catalytic activity
A
False
23
Q
After binding to CDKs, what eventually happens to cyclins?
A
Get degraded by cytoplasmic enzymes, deactivating the CDKs
24
Q
Cyclin-CDK complexes are unique to:
A
Each cell cycle phase
25
Cyclin-CDK complexes activate:
Specific genes to drive cells through the cell cycle
26
Cyclin A can form a complex with which CDK(s)?
CDK 1 and CDK 2
27
Which phase of cell cycle is associated with CDK1 and Cyclin A/B complexes?
Mitosis
28
Cyclin E can form a complex with which CDK?
CDK 2
29
Which phase of cell cycle is associated with CDK2 and Cyclin A/E complexes?
Entry into S phase
30
Cyclin D can form complexes with which CDK?
CDK 4 and 6
31
Entry into G1 phase requires which cyclin/CDK complexes?
CDK4-cyclin D
CDK6-cyclin D
32
Cyclins and CDKs must undergo _____ during the cell cycle
constant cycle of synthesis and degradation
33
Before a cell can progress from one phase of the cell cycle to the next:
it must degrade the cyclin that characterizes that phase of the cell cycle
34
If cyclin is not degraded:
Cell cycle does not continue
35
Favorable conditions for replication
- growth factor signals
- DNA integrity
- cell size
- protein reserves assessed
36
What checkpoint is referred to as the restriction point?
G1
37
What happens at the restriction point?
Cell is committed to division and moves into the S phase
38
If conditions are not favorable during G1 checkpoint:
cell enters **G0 resting state**, await further signals when conditions improve
39
True or false: some cells remain in G0 for lifetime
True - neurons, skeletal muscle cells
40
Transition from G1 to S phase is ruled by: (2)
- CDK4/6-cyclin D (G1 checkpoint)
- CDK2-cyclin E (entry into S phase)
41
What is E2F
transcription factor important for cell growth
42
What happens when E2F is bound to retinoblastoma (Rb) protein?
Production of proteins necessary for G1/S transition is blocked
43
Rb
Retinoblastoma protein
| tumor-suppressor protein/negative regulator of cell cycle
44
How does E2F get released from Rb?
CDK4/6-CyclinD phosphorylates Rb, releasing E2F
45
E2F induces ____ progression in association with ____
S-phase; CDK2-cyclin E
46
Ras protein is a
Proto-oncogene
47
Ras activates:
G1 checkpoint cyclins
48
What happens if Ras protein is mutated?
- Becomes constantly active so will constantly activate G1 cyclins, leading to uncontrolled cell cycle into S phase
- causes cancer
49
____ checkpoint prevents entry into M phase if certain conditions are not met
G2
50
What happens if DNA is not properly replicated/intact during S phase?
- Cell cycle is **paused at G2 checkpoint**
- cell will attempt to **complete DNA replication** or **repair the damaged DNA**
51
Forkhead box M1 protein
transcription factor that allows for **transition to M phase**
| activates expression of FoxM1 target genes
52
In order for FoxM1 to become active, what needs to happen?
Needs to get phosphorylated by CDK2-cyclin A and CDK2-cyclin E
53
M checkpoint also known as
Spindle checkpoint
54
What are the mitotic CDK's?
CDK1-cycin A, CDK1-cyclin B
55
G1/S phase CDKs are inhibited by
Mitotic CDKs
56
When mitotic CDKs are high during M phase, what happens?
factors that initiate DNA replication are inhibited
| 2nd DNA synthesis stopped til mitosis is complete/passes G1 checkpoint
57
Mitotic CDKs activate:
APC/C
58
APC/C function
allow chromatids to separate at anaphase and complete mitosis
59
___ decreases the possibility to aneuploidy
APC/C
60
Negative regulators of the cell cycle- function
Halt the cell cycle
61
Cyclins/CDKs are negatively regulated by
Cyclin-dependent kinase inhibitors (CKIs)
62
Examples of negative regulators of the cell cycle
- INK4 protein inhibitors of CDK4
- CDK-interacting proteins
- E3 ubiquitin enzyme
- tumor suppressor proteins (p53, p21, Rb)
63
Tumor suppressor proteins act primarily at the
G1 checkpoint
64
True or false: tumor suppressor proteins are often mutated/damaged in cancer cells that replicated uncontrollably
True
65
p53 function
halts cell cycle if **damaged DNA is detected**, recruits enzymes to repair the DNA
66
Where is p53 found
In almost every cell
67
p21 function
enforces the halt dictated by p53 by **inhibiting the activity of CDK/cyclin complexes**
68
Rb binds to E2F transcription factor to:
block production of proteins needed for G1/S transition
69
Many anti-cancer drugs act at the level of
Cell cycle signaling pathways
70
1st and 2nd generation anticancer drugs inhibit
Range of CDKs
71
3rd gen anticancer drugs
Specific inhibitors of CDK4 and CDK6 (G1 CDKs)
72
Side effects of anticancer drugs
- neutropenia
- thrombocytopenia
73
Even though we have many different cell types and organs:
All cells have the same genome
74
What gives a cell its unique properties?
Different cells express different RNA transcripts and proteins due to gene regulation
75
Central dogma
DNA to RNA to protein
76
Genome is ____-specific
Species
77
Exome
- entire collection of RNA molecules
- different in different tissues
78
Proteome
Total collection of proteins in a cell
79
_____ are always transcribed in all cell types
Housekeeping genes
80
Examples of housekeeping genes
genes needed for DNA polymerases, metabolism proteins
81
Specialized genes involve those which transcription is:
either on or off in certain cells
| Hb only expressed in RBC
82
Finely tuned genes can ____ in response to external signals
Change expression
83
The set of genes expressed in a cell determines:
the set of RNAs and functional proteins it contains, giving it unique properties
84
Many genes are regulated primarily at the level of:
transcription
85
DNA normally exists as:
Chromatin/chromosomes
86
How is chromatin formed?
When DNA wraps around histone/non-histone proteins
87
Euchromatin
lightly packed, transcriptionally active
88
Heterochromatin
Highly condensed, transcriptionally inactive
89
What is the first stage of DNA compaction?
Nucleosome
90
Methods of epigenetic modification
- DNA methylation
- Histone modifications
91
What adds methyl group to DNA molecule?
DNA methyltransferase enzyme
92
True or false: DNA methylation occurs anywhere on a DNA molecule
False - on CpG dinucleotide
93
DNA methylation forms
5-methyl-cytosine
94
DNA methylation acts as a signal/marker for:
other proteins that read the modification that then recruit other proteins who can modify the histones
95
Histone proteins found in nucleosome
2 each of:
- H2A
- H2B
- H3
- H4
96
Nucleosomes are further packed together by
- histone N-terminal tails
- histone H1 molecules
97
Chromatin blocks access of
Transcription factors to potential DNA binding sites
98
Changes in chromatin structure play a major role in:
regulating gene expression and DNA replication
99
Mechanisms of changing chromatin structure
- enzymatic modification of the histone N-terminal tails
- ATP-driven chromatin remodeling complexes (ATP hydrolysis)
100
Modifications of histone proteins include:
- acetylation
- methylation
- phosphorylation
101
Histone acetylation is done by
Histone acetyl transferase (HAT)
102
Histone methylation is done by
Histone methyl transferase (HMT)
103
Removal of acetyl groups of histones is done by
Histone deacetylase complex transferase (HDAC)
104
Histone code
pattern of histone modifications; has specific meanings
105
Methylation function
usually promotes heterochromatin formation to **silence DNA transcription and gene expression**
106
ATP driven chromatin remodeling complex is thought to
Push on the DNA and loosen the attachment to the histone core, **encourages transcription**
107
Gene regions include
- coding region (introns and exons)
- 5' UTR
- 3' UTR
108
Promoter
region upstream from a gene which is a binding site for transcription factors, RNA polymerase, etc
109
Regulatory sequences
binding sites on DNA for various transcription factors
110
Outcomes of transcription factors binding to DNA
Enhance, diminish, silence the transcription of a gene
111
Where is regulatory sequence located relative to the associated gene?
At a distance
112
Genetic switch
Transcription can be turned on and off in response to a variety of signals
113
Components of a genetic switch
- specific DNA sequences
- proteins that bind to these DNA sequences
114
Other names for transcription factors
- DNA binding proteins
- Gene regulatory proteins
115
Specific transcription factors recognize:
specific DNA consensus sequences
116
Transcription factors contain _____ that can read DNA sequences
Structural motifs
117
Examples of transcription factors structural motifs
- helix-turn-helix proteins
- zinc finger proteins
- leucine zipper proteins
118
Transcription factors read ___ of DNA helix
outside of
119
Positive control
| transcription factors
When TFs bind to DNA and turn gene transcription on
120
Negative control
| transcription factors
When TFs bind to DNA and turn transcription off
121
Negative control TFs are known as
Repressors/gene repressor proteins
122
True or false: TFs can function as activators or repressors or both on different genes
True
123
True or false: A single type of TF can regulate the expression of different genes
True
124
TFs can form ____ and ____ proteins
Homomeric; heteromeric
125
Combinatorial Gene Regulation
Different combinations of TFs can give rise to different cell/tissue types (ex. in development)
126
____ are critical for development
Transcription factors
127
Mutations in TF PAX9 results in
Partial/total anadontia
128
Mutations in TF RUNX2 causes
Supernumerary teeth
129
TATA box
- Gene promoter
- consensus sequence of TATAA/TAA/T
- -30 upstream to gene transcription start site
130
Before transcription can begin:
RNA polymerase II requires general transcription factors to assemble at the promoter
131
Once TFs are recruited:
- recruits RNA Pol II to promoter
- position and help RNA Pol bind to promoter
132
Initiation of transcription
- DNA is pulled apart (helicase activity)
- RNA Pol phosphorylated
133
Post transcriptional control of gene expression methods
- attenuation
- RNA processing
- RNA transport
134
Attenuation
- 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
Pre-mRNA
primary mRNA transcripts in the nucleus
136
RNA transcript processing involves
- 5' capping
- 3' polyadenylation
- splicing
137
When does RNA processing occur
As soon as transcript is being made
138
Exon-intron junctions contain
Consensus sequences (where splicing happens)
139
GU-AG rule
mRNA splicing - GU at 5', AG at 3'
140
Spliceosome
complex of small nuclear RNA (snRNA) and ribonucleoproteins
141
Lariat
Loop structure resulting from cut 5' end of intron that links to adenine
142
Intron is removed as a shape of a
Lariat
143
Splicing makes genes more
Modular - allows new combinations of exons to be created
144
Alternative splicing gives rise to
Different proteins rising from single mRNA transcript
145
Example of a gene that undergoes alternative splicing
- Tropomyosin gene
- amelogenin gene (exon 4 inclusion detrimental to enamel matrix formation)
146
Alternative exon splicing can cause disease such as in:
abnormal processing of the beta globin transcript in beta thalassemia
| mutations can give rise to abnormal exon splicing
147
Alternative splicing can be regulated by
Activator and repressor proteins
148
Where are RNAs transported from/to
From nucleus to cytoplasm
149
Where is mRNA processed
In nucleus before leaving for cytoplasm
150
RNA exits via
Nuclear pore complexes that cover the nuclear membrane
151
The amelogenin gene is composed of ____ exons
7
(inclusion of 4 deleterious to enamel production)
