Final Exam Flashcards

1
Q

function and components of lac operon system

A
  • regulatory system in bacteria
  • controls the expression of genes involved in lactose metabolism
    Components:
    1. Regulatory gene (laCl)
    2. Promoter region
    3. Structural genes (lacZ, lacY, lacA)
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1
Q

Regulatory gene (laCl)

A
  • encodes the lac repressor protein
  • lac repressor binds to the operator region of the lac operon in the absence of lactose, preventing RNA polymerase from binding to the promoter and initiating transcription of the structural genes
  • undergoes an allosteric change upon binding to lactose, causing it to release from the operator region and allow transcription of the structural genes when lactose is present
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2
Q

promoter region (lac operon system)

A
  • DNA sequence upstream of the lac operon that serves as the binding site for RNA polymerase
  • RNA polymerase binds to the promoter and initiates transcription of the structural genes lacZ, lacY, and lacA in the presence of lactose and when the lac repressor is not bound to the operator
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3
Q

Influence of Glucose and/or lactose on Gene expression (lac operon system)

A
  • glucose is present and lactose is absent, the lac operon is typically repressed, even in the presence of lactose
  • Glucose inhibits the production of cyclic AMP (cAMP), which is required for the activation of the lac operon
  • lactose is present and glucose is absent, lactose acts as an inducer of the lac operon
  • RNA polymerase can bind to the promoter, allowing transcription of the lacZ, lacY, and lacA gene
  • both glucose and lactose are present, the lac operon is subject to both catabolite repression and induction. In this case, glucose repression takes precedence, and the lac operon remains repressed
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4
Q

Leaky Scanning and impact on protein sequences

A
  • leaky scanning is when ribosome may bypass 1st AUG start codon and initiate downstream at another AUG
  • can occur if 1st AUG is followed by suboptimal Kozak sequence that weakens recognition by the ribosome
  • can cause synthesis of shorter proteins, lacking amino acids
  • can influence N-terminal sequence, altering stability and function
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5
Q

Prokaryote translation intiation

A
  • small ribosomal subunit bins to Shine-Dalgano sequence on mRNa that is located upstream of start codon
  • initiation factors recruit initiator tRNA to start codon
  • large ribosomal subunit joins complex and forms functional ribosome
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6
Q

eukaryote translation initiation

A
  • formation of PIC, consists of small ribosomal subunit, eukaryotic initiation factors (elFs), initiator tRNA and mRNA
  • PIC binds to 5’ cap of mRNA via elFs and scans mRNA until finds start codon, triggers recruitment of large ribosomal subunit and formation of functional ribosome
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7
Q

polysome formation in prokaryotes

A
  • common and efficient
  • ribosomes quickly bind to mRNA as it is being synthesized by RNA pol
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8
Q

polysome formation in eukaryotes

A
  • more dynamic and regulated
  • mRNA undergoes processing before exported for translation
  • regulatory elements can affect
  • responsive to cellular and environmental cues
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9
Q

How 2 diff proteins evolved to contain same domain

A
  • due to domain shuffling
  • genes undergo recombination events
  • diff parts of genes get mixed which can lead to creation of new genes containing combos of domains from pre-existing genes
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10
Q

protein domain

A
  • structural and functional unit in protein molecule
  • folds independently
  • maintains specific 3D structure that usually performs a specific function
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11
Q

protein domain relation to protein folding

A
  • since they fold independently, they can facilitate folding of entire protein molecule
  • folding of protein domain is facilitated by interactions between amino acids
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12
Q

protein domain relation to functions

A
  • each type of domain performs specific biochemical or structural role
  • proteins often contain multiple domains that each contribute to diff aspects of overall function
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13
Q

protein domain and relation to gene evolution

A
  • evolution of genes often involves acquisition, duplication, deletion, or rearrangement of domains
  • when existing domains combined in new way, can lead t0 proteins with new functions
  • can also undergo mutation
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14
Q

function of promoters

A

DNA sequences located upstream of genes that serve as binding sites for RNA polymerase, initiating the process of transcription

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15
Q

weak promoters

A

have sequences that deviate from the consensus sequence, resulting in less efficient transcription initiation

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16
Q

strong promoters

A

have sequences that closely match the consensus sequence recognized by RNA polymerase, leading to efficient transcription initiation

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17
Q

repressors

A
  • proteins that bind to specific DNA sequences called operators, blocking the binding of RNA polymerase and thereby preventing transcription of the associated genes
  • They negatively regulate gene expression by inhibiting transcription initiation
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18
Q

activators

A
  • proteins that enhance the binding of RNA polymerase to the promoter region, facilitating transcription initiation.
  • They positively regulate gene expression by promoting transcription
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19
Q

operators

A
  • short DNA sequences located adjacent to or overlapping with promoters
  • serve as binding sites for repressor proteins.
  • When a repressor protein binds to the operator, it physically obstructs RNA polymerase from binding to the promoter, leading to repression of gene expression.
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20
Q

activator binding site

A
  • DNA sequences located near the promoter region that serve as binding sites for activator proteins.
  • When an activator protein binds to its binding site, it enhances the recruitment and activity of RNA polymerase at the promoter, thereby promoting gene expression
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21
Q

ligands

A
  • small molecules that bind to regulatory proteins, altering their conformation and activity
  • can act as inducers or co-repressors, modulating the activity of regulatory proteins such as repressors or activators
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22
Q

allosteric regulation

A

the regulation of a protein’s activity by the binding of an effector molecule to a site other than the active site

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23
Q

differential gene expression

A
  • refers to the phenomenon where different cells or tissues within an organism express distinct sets of genes, leading to diverse phenotypes and functions
  • This regulation allows cells to respond to developmental cues, environmental stimuli, and metabolic demands by selectively activating or repressing specific genes
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24
Q

genomic equivalence

A

refers to the concept that all cells within an organism contain the same genetic information or genome, regardless of their specialized functions or developmental stage

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25
Q

evidence for differential gene expession

A
  1. Cell-Type-Specific Gene Expression: For example, neurons express genes encoding neurotransmitter receptors and ion channels, while muscle cells express genes encoding contractile proteins
  2. Developmental Regulation: During development, gene expression patterns change dynamically as cells differentiate into specialized cell types
  3. Environmental response: For instance, the expression of heat shock proteins increases in response to elevated temperatures, aiding in cellular stress response and survival
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26
Q

evidence for genomic equivalence

A
  1. Somatic Cell Nuclear Transfer (cloning):demonstrate that the nucleus of a somatic cell, which has undergone differentiation and expresses tissue-specific genes, can be transferred into an enucleated egg cell. This results in the development of a whole organism with the same genetic material as the donor somatic cell
  2. Cellular reprogramming: Studies on induced pluripotent stem cells (iPSCs) have shown that differentiated somatic cells can be reprogrammed into a pluripotent state by overexpressing key transcription factors.
  3. Transcriptional profiling: Genome-wide transcriptional profiling studies have revealed that all cells within an organism share a common set of genes, known as the core transcriptome
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27
Q

stem cells

A
  • undifferentiated cells with the unique ability to self-renew and differentiate into specialized cell types.
  • serve as the foundation for the development and maintenance of tissues and organs throughout an organism’s life
  • can be classified based on their potency or differentiation potential, which determines their ability to differentiate into various cell types
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28
Q

pluripotent stem cells

A

have the capacity to differentiate into cells of all three germ layers: ectoderm, endoderm, and mesoderm

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29
Q

multipotent stem cells

A

can differentiate into a limited range of cell types within a particular tissue or lineage.

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30
Q

unipotent stem cells

A
  • can only differentiate into one specific cell type
  • They are committed to a particular lineage and serve to replenish and maintain the tissue in which they reside
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31
Q

commitment

A

refers to the irreversible commitment of a stem cell to a particular lineage or differentiation pathway

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32
Q

differentiated cells

A
  • are the end products of the differentiation process
  • have lost the ability to self-renew and typically have a more limited differentiation potential compared to stem cells
  • exhibit specialized functions and are often organized into tissues and organs to perform specific physiological roles
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33
Q

differentiation

A
  • process by which stem cells undergo specialization and become more specialized cell types with distinct functions and characteristics. - cells acquire specific morphological, biochemical, and functional features that enable them to perform specialized roles within tissues and organs
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34
Q

Expressing a protein and amplification

A
  • involves amplification at both transcriptional and translational levels
    transcriptional amplification: increase number of mRNA transcripts synthesized from the gene
    translational amplication: increases number of protein molecules syntehsized from each mRNA transcript
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35
Q

reporter genes and gene regulation

A
  • genes that encode easily detectable proteins or enzymes whose expression levels can be used as indicators of the activity of regulatory elements controlling the expression of another gene of interest
  • are often fused to the promoter region or regulatory sequences of the gene of interest, creating a reporter construct
    -activity of the regulatory elements can be assessed by measuring the expression level of the reporter gene
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36
Q

deletion mapping and gene regulation

A
  • systematically deleting or mutating specific regions of a gene or its regulatory sequences to identify functional elements and determine their roles in gene regulation
  • effects of deletions on gene expression are assessed by comparing the expression levels of the wild-type gene with those of the deletion mutants
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37
Q

how nucleosomes impact binding and contribute to gene regulation

A
  • positioning and density of nucleosomes along the DNA influence the accessibility of specific DNA sequences
  • can either block or facilitate the binding of DNA-binding proteins depending on their positioning relative to the target site
  • Remodeling complexes can evict or reposition nucleosomes to expose DNA sequences that are otherwise inaccessible, allowing DNA-binding proteins to access their target sites and regulate gene expression
  • Histone modifications can influence the recruitment and activity of DNA-binding proteins, including transcription factors, by modulating chromatin accessibility and the binding affinity of these proteins for their target sites
  • positioning of nucleosomes relative to gene regulatory elements, such as promoters, enhancers, and silencers, can impact gene expression
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38
Q

cis regulatory elements

A
  • DNA sequences located adjacent to or within the gene they regulate. - They exert their regulatory effects in a localized manner
    Examples of cis-regulatory elements include promoters, enhancers, silencers, and insulators
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39
Q

trans regulatory elements

A

regulatory factors, such as transcription factors and RNA-binding proteins, that are encoded by genes located elsewhere in the genome
- They act in trans, meaning they can influence the expression of target genes located at different genomic
loci
- modulating gene expression by binding to specific cis-regulatory elements and regulating transcriptional activity

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40
Q

co-regulatory networks

A
  • Transcription factors can form complex regulatory networks by interacting with co-regulatory proteins, such as co-activators and co-repressors, to modulate gene expression.
  • Co-regulatory proteins can enhance or inhibit the transcriptional activity of transcription factors by influencing chromatin structure, promoting protein-protein interactions, and facilitating the assembly of transcriptional complexes
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41
Q

mechanisms to stably maintain gene expression patterns in a given cell or cell lineage

A
  1. epigenetic modifications
    - Histone modifications can alter chromatin structure and accessibility, influencing gene expression patterns
    - epigenetic marks are inherited by daughter cells
  2. chromatin remodeling complexes
    - can reposition, evict, or modify nucleosomes, influencing the accessibility of regulatory elements and the transcriptional activity of target genes
    - ensuring the fidelity of chromatin structure and the transmission of epigenetic information to daughter cells
  3. regulatory feedback loops
    - can stabilize gene expression patterns by providing buffering mechanisms that counteract fluctuations in gene expression levels and maintain homeostasis
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42
Q

how mechanisms of gene regulation could allow coordinated expression of groups of genes during development or in response to external stimuli

A
  • non-coding RNAs : miRNAs can target multiple genes within the same pathway or functional module, leading to coordinated regulation of gene expression
  • signaling pathways: can converge on transcription factors and co-regulators, leading to the coordinated regulation of target genes
  • transcriptional networks: integrate signals from multiple pathways and coordinate the expression of genes involved in specific biological processes or responses
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43
Q

transcriptional regulation

A
  • involves controlling the initiation of transcription from DNA to RNA by RNA polymerase.
  • Key regulatory elements involved in transcriptional regulation include promoters, enhancers, silencers, and transcription factors
  • allows cells to control which genes are transcribed and at what levels, providing a rapid and reversible mechanism for modulating gene expression
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44
Q

post-transcriptional regulation

A
  • refers to the regulation of gene expression after mRNA synthesis, involving processes that affect mRNA stability, processing, and translation
  • Key mechanisms of post-transcriptional regulation include alternative splicing, mRNA stability, mRNA localization, microRNA (miRNA) regulation, and translational control
  • involves regulating the rate at which mRNA molecules are translated into proteins
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45
Q

components of a eukaryotic gene

A
  1. enhancer/silencer
  2. promoter
  3. 5’ UTR
  4. Exon
  5. Intron
  6. 3’ UTR
  7. Start codon
  8. Stop codon
  9. transcriptional initiation and terminations site
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46
Q

3’ UTR

A

Location: Following the last exon and before the transcription termination site.
Function: The 3’ UTR contains regulatory elements involved in mRNA stability, localization, and translational regulation.

47
Q

5’ UTR

A

Location: Between the transcription start site and the translation start codon (usually AUG).
Function: The 5’ UTR contains regulatory elements that influence translation efficiency and mRNA stability

48
Q

how alternative splicing can be regulated

A
  • Transcriptional regulation can influence alternative splicing by modulating the abundance or activity of RNA-binding proteins (RBPs) and splicing factor
  • RBPs play key roles in alternative splicing regulation by binding to specific sequences within pre-mRNA transcripts and modulating splice site selection
  • splicing factor availability
  • Mutations or sequence variations within these cis-elements can disrupt splicing regulation and lead to aberrant splicing patterns
  • Changes in chromatin structure can alter the recruitment of splicing regulators and impact splice site selection
49
Q

why some alternative splicing can be constitutive

A

constitutive: occur in a consistent and predictable manner across different cell types or conditions
- structural organization of certain genes and their associated regulatory elements may favor constitutive alternative splicing
- Genes involved in essential cellular functions, often referred to as housekeeping genes, may undergo constitutive alternative splicing to generate mRNA isoforms with different functions or regulatory properties

50
Q

nonsense mediated decay

A

quality control mechanism that recognizes and degrades mRNA transcripts containing premature termination codons (PTCs) to prevent the production of truncated or potentially harmful proteins

51
Q

steps of nonsense mediated decay

A
  • ecognition of a premature termination codon (PTC) within the mRNA transcript
  • presence of a PTC downstream of an EJC triggers the recruitment of NMD factors, including UPF1 (up-frameshift 1), UPF2, and UPF3, to the aberrant mRNA transcript. UPF1 interacts with the EJC and ribosomal release factors, leading to the activation of downstream NMD effectors
  • UPF1 recruits additional NMD factors and ribonucleases, forming ribonucleoprotein complexes involved in mRNA degradation
51
Q

covalent modification of mRNA and influence on amount and amino acid sequence of a protein

A
  • can affect the stability of mRNA transcript, which can alter the abundance of mRNA transcripts available for translation, thereby influencing protein expression levels
  • affecting the accessibility of mRNA transcripts to ribosomes and translation initiation factors
  • can affect the recognition of splice sites and the activity of splicing factors, leading to changes in the splicing patterns of mRNA transcripts
  • Changes in the nucleotide sequence of mRNA due to RNA editing can result in the production of proteins with altered amino acid sequences
52
Q

importance of mRNA localization

A
  • plays a critical role in establishing and maintaining spatial patterns of gene expression during development.
  • Local translation of synaptic mRNAs regulates the strength and stability of synaptic connections, synaptic transmission, and synaptic remodeling
  • can facilitate rapid responses to stress or environmental changes by directing the synthesis of stress-responsive proteins to specific subcellular compartments
  • localized translation, cells can efficiently synthesize proteins where they are needed, minimizing energy expenditure and optimizing cellular function
53
Q

mechanisms for regulating mRNA localization

A
  • RNA-binding proteins bind to specific RNA sequences or structures within mRNA transcripts and mediate their localization to subcellular compartments
  • Localization signals within mRNA molecules recognized by RBPs, which then transport the mRNA to its destination
54
Q

mechanisms that could result in different versions of a protein expressed (from the same gene) in different cells

A
  1. alternative splicing: allows different combinations of exons within a pre-mRNA transcript to be spliced together,
  2. Differences in mRNA localization and transport between different cell types can result in cell-type-specific protein synthesis from the same gene
  3. Differences in post-transcriptional regulation can lead to differential expression of mRNA isoforms and protein variants from the same gene in different cells
  4. Differences in epigenetic regulation between different cell types can impact transcriptional activity at a gene locus, resulting in differential expression of mRNA isoforms and protein variants
  5. post-translation modifications can modulate function, localization, and stability of proteins
  6. Activation of cell-type-specific signaling pathways can result in differential regulation of gene expression and protein synthesi
55
Q

maternal contributions

A

refer to the molecules, such as mRNA and proteins, present in the egg or embryo that are derived from the mother and play essential roles in early embryonic development

56
Q

p-bodies

A
  • play important role in regulating mRNA metabolism, particularly in response to cellular stress
  • sites of mRNA decay and contain enzymes and proteins involved in mRNA degradation pathways
  • also serve as sites for mRNA storage and surveillance, where untranslated or stalled mRNAs can accumulate temporarily before being degraded or returned to the translation pool
57
Q

stress granules

A
  • play important role in regulating mRNA metabolism, particularly in response to cellular stress
  • sequester untranslated mRNAs and translation initiation factors, preventing their engagement in translation and allowing cells to prioritize stress response pathways over general protein synthesis
58
Q

intracellular signaling pathways

A
  • transmit signals from receptors located within the cell
  • receptors can be activated by intracellular ligands, such as second messengers or changes in ion concentrations
    Examples include cyclic AMP (cAMP) signaling pathway, calcium signaling pathway, and MAP kinase cascades.
59
Q

cell-surface receptor mediated signaling pathways

A
  • involve receptors located on the cell surface that bind to extracellular ligands, such as hormones or growth factors
  • Upon ligand binding, these receptors initiate signaling cascades within the cell
    Examples include receptor tyrosine kinase (RTK) pathways, G protein-coupled receptor (GPCR) pathways, and cytokine receptor pathways.
60
Q

ligand-activated signaling pathways

A
  • initiated by the binding of extracellular ligands to cell surface receptors
  • Ligand binding induces conformational changes in the receptors, leading to the activation of downstream signaling cascades.
    Examples include growth factor signaling pathways (e.g., insulin signaling via insulin receptor), cytokine signaling pathways, and neurotransmitter signaling pathways
61
Q

stress-activated signaling pathways

A
  • triggered in response to various cellular stresses, such as oxidative stress, DNA damage, or nutrient deprivation
  • pathways help cells adapt to adverse conditions and maintain cellular homeostasis.
    Examples include p38 MAP kinase pathway, c-Jun N-terminal kinase (JNK) pathway, and unfolded protein response (UPR) pathway.
62
Q

general features of signal transduction

A
  • begins with the binding of an extracellular signaling molecule (ligand) to a specific receptor on the cell surface or within the cell
  • receptor undergoes a conformational change that activates its intracellular signaling domain or recruits downstream signaling molecules to the receptor complex
  • signal is transmitted from the cell surface or receptor to intracellular signaling proteins or complexes,
  • Intracellular signaling molecules, phosphorylate downstream effector proteins
  • signals from multiple receptors or pathways can converge and be integrated at various points in the signaling network
  • intracellular signal ultimately leads to changes in cellular behavior, gene expression, or metabolism, collectively known as the effector response
63
Q

regulation by long non-coding RNA (lncRNA)

A
  • can interact with chromatin-modifying complexes, transcription factors, and other regulatory proteins to modulate gene expression
  • transcriptional regulation, chromatin modification, mRNA stability, and post-transcriptional regulation
  • involved in X chromosome inactivation
64
Q

regulation by microRNA

A

regulate gene expression post-transcriptionally by binding to complementary sequences in the 3’ untranslated regions (UTRs) of target mRNAs, leading to mRNA degradation or translational repression

65
Q

regulation by small interfering RNA

A
  • involved in RNA interference (RNAi), a conserved mechanism for silencing gene expression at the post-transcriptional level
  • mediate sequence-specific mRNA degradation by guiding the RNA-induced silencing complex (RISC) to target mRNAs for cleavage
66
Q

regulation by CRISPR RNA

A
  • component of the CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated)
  • rRNAs guide Cas proteins to target and cleave foreign nucleic acids, such as viral or plasmid DNA
67
Q

how CRISPR/Cas9 can be used for genome editing

A
  • CRISPR/Cas9 consists of a guide RNA (gRNA) that directs the Cas9 nuclease to a specific target DNA sequence through base-pairing interactions.
  • The Cas9 nuclease induces double-strand breaks (DSBs) at the target site, which triggers DNA repair mechanisms.
68
Q

how/why homology-directed repair vs NHEJ would be used with CRISPR

A
  • For gene knockout: NHEJ-mediated gene knockout is commonly used to disrupt gene function by inducing frameshift mutations or premature stop codons
  • For gene correction: allows for precise correction of disease-causing mutations by introducing specific sequence changes at the target site
69
Q

features of a disease may make it a good candidate for CRISPR/Cas9 gene editing therapy

A
  • Diseases caused by mutations in a single gene
  • Diseases with a well-characterized genetic basis
  • Diseases with severe phenotypes and significant morbidity or mortality
  • Diseases affecting tissues or organs that are accessible to CRISPR/Cas9 delivery methods,
70
Q

Yamanka factors and regenerative medicine

A
  • set of transcription factors that can reprogram differentiated adult cells into induced pluripotent stem cells (iPSCs)
  • iPSCs can be generated from a patient’s own somatic cells, such as skin cells or blood cells. These patient-specific iPSCs can then be differentiated into various cell types for regenerative therapies, bypassing issues of immune rejection and ethical concerns associated with embryonic stem cells
71
Q

X inactivation steps

A
  • initiation of XCI is regulated by the X-inactivation center (Xic), a region on the X chromosome that contains genes involved in XCI, including Xist
  • Xist gene is upregulated
  • Xist RNA, a long non-coding RNA, coats the future Xi in cis and spreads along the length of the chromosome.
  • recruits chromatin-modifying complexes, leading to the formation of repressive chromatin domains and transcriptional silencing of genes on the Xi
  • Xi becomes condensed and forms a dense, heterochromatic structure known as the Barr body
72
Q

which RNA molecules are commonly covalently modified

A
  1. messenger RNA
  2. transfer RNA
  3. ribosomal RNA
73
Q

functional consequences of covalent RNA modification

A
  • an influence translation initiation, elongation, and termination processes, thereby regulating protein synthesis
  • RNA stability
  • can alter RNA secondary and tertiary structures, affecting RNA-protein interactions, RNA folding, and RNA-based regulatory mechanism
  • cellular signaling
74
Q

scaffold proteins

A
  • molecules that serve as structural frameworks or platforms for organizing multi-protein complexes involved in signaling pathways.
  • play a crucial role in signal transduction by bringing together specific signaling components into close proximity
75
Q

adaptor proteins

A
  • molecules that link together different signaling components by mediating protein-protein interactions
  • facilitating the assembly of multi-protein signaling complexes and promoting cross-talk between different signaling pathways.
76
Q

interaction domains

A
  • specific regions or motifs within proteins that mediate protein-protein interactions
  • play a critical role in signal transduction by facilitating the formation of protein complexes and the transmission of signals between signaling molecules
77
Q

common characteristics of cancer

A
  • uncontrolled cell growth
  • resistance to cell death
  • immortality
  • genomic instability and mutation
  • evading immune destruction
78
Q

how phosphorylation can create molecular switches that regulate protein binding and catalytic activity

A
  • directly affecting the binding affinity between proteins or by inducing conformational changes that expose or conceal protein interaction surfaces
  • regulate enzyme activity
    mechanism for temporal and spatial - regulation of protein function by allowing rapid and reversible changes in protein activity in response to cellular cues or environmental stimuli
79
Q

how a western blot could be used to study protein levels and cell signaling

A
  • Western blotting allows for the visualization of target proteins using specific antibodies.
  • The intensity of the protein bands on the Western blot can be quantified using imaging software, providing a semi-quantitative or quantitative assessment of protein expression levels
80
Q

Receptor Tyrosine Kinases (RTKs)

A
  • activated by binding of extracellular ligands
  • induces conformational changes in the receptor
81
Q

ligand gated channels (LGCs)

A
  • ion channels that are activated by binding of specific ligands, such as neurotransmitters or hormones, to their extracellular domains
  • binding induces conformational changes in the channel protein, leading to opening of the ion channel pore and influx or efflux of ions across the plasma membrane
82
Q

G protein coupled receptors (GPCRs)

A
  • activated by binding of extracellular ligands, such as hormones, neurotransmitters, or odorants, to their extracellular domains
  • induces conformational changes in the receptor, leading to activation of associated heterotrimeric G proteins by promoting GDP-GTP exchange on the Gα subunit
83
Q

non-receptor kinases

A
  • activated by various mechanisms, including phosphorylation, conformational changes, or binding to specific regulatory proteins
84
Q

GTPases

A

activated by binding of GTP (guanosine triphosphate) to their active site, leading to a conformational change that enables interaction with downstream effectors

85
Q

oncogene

A
  • gene that has the potential to cause cancer when it is mutated or overexpressed
  • encode proteins that regulate various aspects of cellular processes, when mutated or overexpressed, oncogenes can drive uncontrolled cell growth and contribute to the development and progression of cancer
  • associated with gain-of function mutations, lead to increased protein activity or expression
86
Q

tumor suppressor

A
  • gene that plays a critical role in preventing cancer by regulating cell proliferation, survival, and genomic stability
  • encode proteins that act as negative regulators of cell cycle, help maintain genomic integrity and prevent the development of cancer by suppressing the growth of abnormal or damaged cells
  • associated with loss of function mutations
87
Q

viral oncogene

A
  • gene derived from a virus that has the potential to induce cellular transformation and promote cancer development
  • often incorporated into the host cell’s genome as a result of viral infection and can lead to dysregulation of cellular processes, including cell proliferation, survival, and differentiation.
88
Q

Viral oncogenes play a crucial role in the study of cell signaling proteins and pathways for several reasons:

A
  • often encode proteins that mimic or hijack cellular signaling pathways, by studying the effects of viral oncogenes on host cell signaling, researchers can identify key signaling proteins and pathways involved in cancer development and progression
  • Viral oncogenes can serve as probes to identify novel signaling proteins and potential therapeutic targets for cancer treatment
89
Q

second messengers

A
  • small molecule that serves as an intermediary in cell signaling pathways, transmitting signals from cell surface receptors to intracellular effector proteins
  • typically generated in response to the activation of cell surface receptors, such as G protein-coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs), and they propagate the signal by activating downstream signaling cascades.
90
Q

3 major ways to assemble intracellular signaling complexes

A
  1. Protein-protein interactions: often involve specific protein domains, motifs, or binding sites that mediate the association between signaling components
  2. Scaffolding proteins: platforms for the assembly of signaling components, facilitating efficient signal transduction and integration
  3. Post-translational modifications
91
Q

roles of PI3K and PTEN in regulating Ak

A
  • PI3K phosphorylates PIP2 to PIP3, serves as a second messenger that recruits Akt to plasma membrane
  • Once recruited to the membrane, Akt is phosphorylated and activated
  • PTEN is a lipid phosphatase that counteracts the activity of PI3K by dephosphorylating PIP3 back to PIP2
  • acts as a tumor suppressor by negatively regulating the Akt signaling pathway
92
Q

Philadephia chromosome

A
  • a shortened chromosome 22 resulting from a reciprocal translocation between chromosomes 9 and 22, specifically between the long arms of these chromosome
  • results in the fusion of two genes: fusion gene encodes a constitutively active tyrosine kinase enzyme, which plays a central role in the pathogenesis of chronic myeloid leukemia (CML) by driving uncontrolled cell proliferation and survival
  • discovery provided the first clear evidence linking a specific chromosomal abnormality to a human cancer, prior to this discovery, cancer was generally thought to be a result of uncontrolled cell growth without a clear understanding of its genetic basis
93
Q

what Bcr-Abl is and why it was a good drug target for development of Gleevec

A
  • fusion protein resulting from the Philadelphia chromosome translocation
  • attractive drug target for the development of Gleevec due to its central role in the pathogenesis of CML by driving uncontrolled cell proliferation and survival
94
Q

mechanisms that could lead to activation of an oncogene or suppression/loss of a tumor suppressor

A
  • Oncogenes can be activated by point mutations, can also occur through gene amplification, activated through integration of viral DNA into the host genome
  • Tumor suppressor genes can be inactivated by deletion of one or both copies of the gene or by loss-of-function mutations, can be silenced through epigenetic mechanisms, can be downregulated or inactivated by dysregulation of signaling pathways or transcription factors that control their expression
95
Q

why most people who inherit a mutation in Rb from a parent eventually develop retinoblastoma in both eyes

A
  • “two-hit” hypothesis
  • individuals who inherit one defective copy of the Rb gene (a germline mutation) are predisposed to developing retinoblastoma because they only require one additional somatic mutation (second hit) in the other copy of the Rb gene to completely lose its tumor-suppressing function
96
Q

tumor microenvironment and role in tumor progression

A
  • complex milieu of cells, molecules, and extracellular matrix components that surround and interact with tumor cells within a tumor mass
  • plays a critical role in tumor progression by regulating various aspects of tumor biology, including growth, invasion, metastasis, immune evasion, and response to therapy
97
Q

why inherited mutations in tumor suppressor genes lead to a high incidence of cancer

A
  • when these genes are mutated, their tumor-suppressing activities are compromised
  • Inherited mutations in tumor suppressor genes are present in the germline cells, as a result, every cell in the individual’s body carries the mutated gene
  • Many tumor suppressor genes follow a “two-hit” hypothesis, which posits that both copies of the gene (alleles) must be inactivated or mutated to abolish their tumor-suppressing activities.
98
Q

Non-Homologous End Joining (NHEJ)

A
  • error-prone DNA repair mechanism that rejoins broken DNA ends directly without the need for a homologous template
  • DNA ends are processed by nucleases and then ligated together by DNA ligase IV
99
Q

Homologous Recombination (HR)

A

high-fidelity DNA repair mechanism that uses a homologous DNA template, typically a sister chromatid, to repair DSBs
-involves the formation of a DNA strand invasion intermediate, followed by DNA synthesis using the homologous template and resolution of the Holliday junction

100
Q

general role of cyclins/Cdks and checkpoints in regulating the cell cycle

A
  • regulate cell cycle progression by phosphorylating target proteins involved in key cell cycle transitions
  • Cell cycle checkpoints monitor DNA integrity and other cellular signals, halting cell cycle progression in response to abnormalities
  • Dysregulation of cyclins, Cdks, or checkpoints can lead to uncontrolled cell proliferation, genomic instability, and cancer development
101
Q

R (restriction) point and Rb

A
  • G1 checkpoint or start checkpoint, is a critical regulatory point in the cell cycle that determines whether a cell will progress from the G1 phase to the S phase and commit to DNA replication
  • Rb plays a key role in regulating the R point by inhibiting the activity of E2F transcription factors and controlling the expression of genes required for entry into the S phase
  • Dysregulation of Rb function can lead to aberrant cell cycle progression and contribute to tumorigenesis
102
Q

p53

A
  • tumor suppressor protein that plays a central role in regulating cell cycle progression, DNA repair, apoptosis, and genomic stability.
  • acts as a transcription factor, controlling the expression of genes involved in various cellular processes, including those related to cell cycle arrest, DNA repair, and apoptosis
103
Q

regulation of p53

A
  • Under normal conditions, p53 protein levels are kept low through continuous ubiquitination
  • In response to various stress signals, stabilization and accumulation of p53
  • Stabilized p53 undergoes post-translational modifications, which enhance its transcriptional activity and ability to bind to target genes
  • activated p53 acts as a transcription factor, inducing the expression of genes involved in cell cycle arrest, DNA repair, and apoptosis, thereby promoting cellular responses to stress
104
Q

importance of apoptosis and cell cycle checkpoints in preventing cancer development

A
  • Cell cycle checkpoints are surveillance mechanisms that monitor DNA integrity and ensure the accurate replication and segregation of genetic material during cell division
  • Apoptosis is a tightly regulated process of cell death that eliminates cells with irreparable DNA damage, oncogenic mutations, or other abnormalities
105
Q

mutagen

A

any agent or factor that can induce genetic mutations in DNA, leading to changes in the nucleotide sequence and potentially causing alterations in protein structure or function

106
Q

carcinogen

A

any substance or agent that has the potential to cause cancer by inducing genetic mutations or promoting cellular transformation

107
Q

sporadic cancer

A
  • refers to cancer that arises sporadically without a significant hereditary component
  • typically caused by somatic mutations acquired during an individual’s lifetime due to exposure to environmental factors, lifestyle factors and random errors in DNA replication and repair processes
  • majority of cancers diagnosed in the general population
108
Q

hereditary cancer

A
  • refers to cancer that is caused by inherited genetic mutations passed down from one generation to the next
  • mutations are present in the germline
109
Q

tumor microenvironment

A
  • refers to the cellular environment surrounding a tumor
  • plays crucial roles in tumor growth, invasion, metastasis, and response to therapy
  • can influence tumor progression by promoting angiogenesis, immune evasion, inflammation, and tissue remodeling
110
Q

non mutagenic cancer risk factors

A
  1. chronic inflammation: Prolonged inflammation can promote cancer by creating a microenvironment that fosters tumor growth, invasion, and metastasis.
  2. Hormonal factors: an promote cancer growth by stimulating cell proliferation, inhibiting apoptosis, and altering the expression of genes involved in tumor progression
  3. obesity: Adipose tissue produces hormones and cytokines that promote inflammation, insulin resistance, and cell proliferation, creating a pro-carcinogenic microenvironment
  4. Dietary factors
  5. physical inactivity
111
Q

possible outcomes of p53 signaling

A

can lead to various outcomes, including cell cycle arrest, DNA repair, apoptosis, or senescence

112
Q

Li-Fraumeni Syndrome

A
  • rare hereditary cancer predisposition syndrome caused by germline mutations in the TP53 gene, leading to loss of functional p53 protein.
  • Individuals with LFS have an increased susceptibility to various types of cancer at a young age due to impaired p53-mediated DNA damage response and cell cycle arrest
113
Q

why do elephants have lower cancer risk than humans

A
  • proposed explanation for this lower cancer risk is the presence of extra copies of the TP53 gene
  • additional TP53 gene copies may enhance p53-mediated apoptosis in response to DNA damage or stress, effectively eliminating damaged cells before they can develop into tumors