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180 Cards in this Set

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  • Back
  • 3rd side (hint)
What is the basic unit of DNA (the last fold of DNA) and how may base pairs does it contain?
nucleosome… 160-180 bp
T/F: modification of histone has no effect on gene expression
Enumerate the steps in the transcription of DNA
1. DNA becomes accessible… 2. RNA polymerase associates with DNA… 3. (some proteins in polymerase complex are always seen in transcription some are specific for a particular expression)… 4. enhancer regions can be distal to the site of initiation… 5. enhancer can be more than 100,000 bp away and can control and can control several gene (creates a loop of the DNA)
What is "transcription" by committee?
the array of proteins binding to a gene that determines the amount of transcription that gene will undergo, therefore the availability of these proteins regulate gene expression
T/F: transcription regulation protein work in either a negative or a positive manner
what can make the DNA more suseptible to translation? (Hint: histones)
the histones in a nucleosome can be modified by the addition of an actyl, methyl, phosphate or other group
In the transcription of DNA to mRNA what must be added to the 5' end?
a 7-MeG "Cap" is added, which indicates it's ready to be processed in translation
In the transcription of DNA to mRNA what must be added to the 3' end? And what is its purpose?
a) A poly-A tail is added to the 3' end… b) protect the mRNA from exonases, transcription termination, export from the nucleus, and for translation
Which pre-mRNA is exported for translation?
Is mRNA always ready for translation upon leaving the nucleus?
no, sometimes it must be transported to a particular location
When is translation regulated?
during splicing and polyadenylation
In terms of storage why is splicing important
because one gene can express multiple proteins
Give an example of mRNA being modified.
Apolipoprotein B in tissue specific cells allows for mRNA to undergo addition modification… THIS IS RARE
What is Thalassemia an example of?
Mutation in genes that codes for aberrant process of RNA
T/F: mRNA lifetime is random and essentially the same for all mRNA
false, it is usually determined by the 3' end… in fact aberrant (mutant) can be marked for destruction
What is Nonsense Mediated Decay?
When mutant/aberrant mRNA is identified and destroyed
What is RNAi?
single stranded RNA about 20 nucleotides long, cut from a longer DS RNA that can regulate translation
Where does translation of mRNA proceed and what binds to this region?
5' cap, where intiation factors bind
What codon is the start codon?
What is IRES?
It is a rare site of translation initiation, which is sometimes used by viruses to hijack the translation mechanisms of a cell
What is the function of GTPases such as eIF2, IF2 and EF2?
They ensure that translation progresses forward.
Give the 4 steps in utilization of GTPases in translation, which is uni-directional
1) The protein (eIF2, EF1 or EF2) is complexed with GTP… 2) GAP induces the protein to hydrolyze GTP to GDP… 3) the protein is now complexed GDP with higher affinity than GTP… 4) GEP induces the protein to exchange GDP with GTP.
How is translation regulation mediated?
through the modifications of the GEF responsible for recycling of eIF2
Name the 4 types of mutations in the exon sequences that can lead to altered proteins.
Silent mutations, missense mutations, nonsense mutations, and frame shift mutations.
What is a silent mutation?
When a mutated codon produces the same amino
What is a missense mutation?
when mutated codon produces a different amino acid
What is a nonsense mutation?
when mutated codon is is UAA, UAG or UGA… a stop codon… shortening the protein
What is framshift mutation?
when 1 or two nucleotides are inserted or deleted that resets the reading frame, making the down stream protein different… usually fatal
which type of mutations are used by retroviruses?
retroviruses use frameshift mutations to produce reverse transcriptase.
How many amino acids are coded for by the genetic code?
After accounting for post-transcriptional modification, how many amino acids are found in human proteins?
Finish these post-translational modification to amino acids and name their site of action when asked.

1) proline converted to? Where?

2) addition of _____ ________ to amino acids. Where?

3) the ____________ of serine, thronine or tyrosine in cell regulation

4) the ________, _________, and _______ of histones
1) proline converted to hydroxyproline in collagen, 2) addition of complex sugars to amino acids in the golgi, 3) the phosphorylation of serine, thronine or tyrosine in cell regulation, 4) the acetylation, methylation or or phosphorylation of histones.
Which protein is usually involved in the folding of the one-dimensional polypeptide chain into a complex 3-D shape?
What is a good example of the final protein product being produced by the cutting off of part of the polypeptide chain?
Name 6 generally permanent post translational modification (verify the answer on this one!!!!!!)
hydroxylation, methylation, acetylation, glycosylation, attachment of lipid (seen in membrane), prosthetic groups (e.g., heme)
What type of temporary post-translational modification plays a role in turning a cell on and off?
phosphorylation of serine, threonine, tyrosine, and sometimes histidine
Name 4 temporary post-translational modifications (Verify the answer here)
phosphorylation, acetylation, methylation, and the addition of small proteins, such as ubiquitin (which leads to degradation by proteosomes) or SUMO (small ubiquitin-like modifier)
Are Cleavage, Dimerization (or oligomerization), and Assembly temporary or permanent post-translational modifications.
Name three examples of the cleaving of proteins.
1) membrane or secretory proteins entering the ER have a signal sequence that is cleaved off in the ER… 2) cytoplasmic proteins entering the mitochondria have a targeting sequence removed… 3) cleaving of dangerous molecules, like proteosomes.
Which of the following is an example of a dimerized protein?
a) hemoglobin
b) insulin
Is a ribosome being assembled into a complex machine a permanent post-translational modification?
What is the pathway of most membrane and secretory proteins?
ER to Golgi, traveling by vessicles
What is the function nuclear localization signals?
They lead proteins to the nuclear pores, where they are transported into the nucleus.
What is the function of Nuclear Export Signals (NES)?
They lead to the export of a protein from the nucleus
what effect do the following amino acid modifications have on gene expression? A) methylation of residue 9, B) methylation transferred from residue 9 to N-terminus and acetylation of residue 9 c) phosphorylation of residue 10 and acetylation of residue 14
A) methylation of residue 9, --> gene silencing/ herterochromatin… B) methylation transferred from residue 9 to N-terminus and acetylation of residue 9 --> gene expression… c) phosphorylation of residue 10 and acetylation of residue 14 --> gene expression
What is the main function of DNA?
storage of genetic information
T/F: Transcription factors interact with:1) DNA… 2) chromatin structure associated with DNA… 3) and recruit RNA polymerase II and its associated factors
T/F: it is common for transcription factors to initiate transcription on "closed" chromatin on its own.
FALSE, chromatin is first opened up by modification to histones.
What is the function of Histone Acetyl Transferase (HAT) function
Histone acetyl transferase, modifies histones and open chromatin for transcription
Stop Here
What does the opening of chromatin by BOTH chromatin remodeling factors (e.g., HAT) AND transcription factors say about the nature of the process?
The opening of chromatin by chromatin remodeling factors (e.g., HAT) and transcription factors is COOPERATIVE
Can one or the other open chromatin on its own?
What 2 roles do histone tails play in opening up chromatin?
1) they influence the accessibility and,

2) they affect the binding ability of DNA
What is the role of the TATA box? What is the role of the TATA-box Binding Protein?
a) The TATA box serves as the locator for the site of initiation transcription… b) TBP bends the DNA and helps position the RNA polymerase to initiate transcription
Describe the 4 steps of the binding sequence of the constitutive transcription factors. (Hint: start with TBP)
1) TBP and associated TAFs (TFIID) bind to DNA… 2) TFIIB binds to TFIID & DNA… 3) RNA polymerase II binds to the factors & DNA… 4) Elongation factors bind and transcription commences
Give an example of the constiutive transcription factors recruited by the DNA binding proteins
Leucine Zipper, which holds to proteins together
what are the two parts of the transcription initiation complex?
1) a binding domain that interacts with DNA and 2) an activation domain that interacts with proteins
What is the relationship between an enhancer and an activator? How many enhancer regions are there on a gene… and how many activators are in a transcription factor complex
the enhancer is the region of DNA upstream or downstream where proteins bind to effect transcription… while the activator is the protein that binds to the enhancer region and effects the level of transcription… b) 1 to many of both
Do transcription factors only bind up stream?
No… they can bind both upstream and downstream
Name 3 examples of the mechanisms of gene repression.
1. Competitve DNA binding… 2) Masking the activation surface… 3) direct interaction with the general transcription factors.
Without the presence of an injury, what is suspected in an enlarged spleen in children?
ß-Thalassemia Major
What is the cause of ß-Thalassemia Major?
Insufficient ß globin molecules … transcription factors are often to blame
Give 2 mutational examples of ß-thalassemia caused by an insufficient transcription
1) Cis-mutation (insufficient transcription)… 2) mutation in the mRNA cleavage signal, which results in an extended globin mRNA and this leads to a shortened mRNA globin lifespan
Give 7 examples for activating a transcription factor.
1) protein synthesis… 2) ligand binding… 3) Protein phosphorylation… 4) addition of a second subunit… 5) Unmasking (e.g., release of an inhibitor via phosphorylation)… 6) Stimulation of nuclear entry (e.g., release of an inhibitor)…7) release form membrane
Trace the steps of gene express activation via JAK/STAT.
Interferon activate JAK --> receptor dimerizes --> phosphorylation of STAT (which is a transcription factor) STAT will now migrate into the nucleus to bind specific sequences to activate transcription
What is hnRNA?
pre-mRNA, before m7G is added to 5', adenylation and splicing
What happens to the RNA polymerase II shortly after initiation? What terminus binds the RNA polymerase II?
a) it is phosphorylated and then binds proteins used in RNA processing… b) C-terminal domain
What does adding a 7-methyl G "Cap" do to the 5' end?
it gives the mRNA a 3' OH at both ends... signifies the transcription should begin... designates RNA for export... prevents degradatio by exonucleases
What 4 purposes does the m7G Cap serve?
1) It is the signature of the Poll II transcript… 2) It protects the mRNA from 5' nucleases… 3) Serves as a signal for mRNA export… 4) Serves as a signal for subsequent translation.
How is the 3' end of mRNA formed?
cleavage followed by the adenylation… not by the termination fo the transcript
What is the function of snRNA?
splicing of RNA… intron removing… where the RNA carries out the catalytic steps
What are the 3 key regions of an intron?
5' splice site, 3' splice site and the branch point
What is a spliceosome?
it is a protein that splices exons together
What are the 2 steps in mRNA splicing?
1) Lariat formation and 5' splice site cleavage… 2) 3' splice stie cleavage and joining of the two exon sequences
What happens to the snRNP and the Lariat?
the lariat is degraded and the snRNP is recycled
Where is the Glycine receptor (GlyR∂2) an important inhibitor and what does a mutation in this receptor cause?
CNS: Startle response
What is believed to be the source of alternative splicing?
differential binding of different proteins
T/F: all thalassemia mutations are in the coding regions (exons)
false some are in introns
What is the problem is splicing a in a intron with 19 nucleotides? (CONFIRM THIS!!!!!!!)
It is not divisable by 3 and will thus be out of the reading frame
Why do you see more Apo48 in the intestines than in the liver?
the intestine has more cytidine deaminease,
What is the mechanism for alternatively forming Apo48 form instead of Apo100 form of protein?
Cytidine deaminase converts a C, via deaminated, to a U, which results in a stop codon so Apo40, which is shorter than Apo100, is formed
What is the function of Apo100 and Apo48?
Apo48 transports fats from the intestines to the tissues, while Apo100 delivers cholesterol to cell via LDL receptors.
Which is the first ribosomal subunit that binds to mRNA?
What are the 2 key initiation factors in translation.
1)eIF4, which binds the CAP, and signifies the RNA is to translated… 2) eIF2, which binds the Met tRNAi and the 40s subunit and GTP
a) What inactivates eIF4 in tumor formation? How?
b) How does Poliovirus inhibit translation of host proteins? (hint?)
c) Given the function of ______, how does poliovirus RNA translated?
a) eIF4-BP, via phosphorylation of eIF4-BP (found in tumor cells)
b) by cutting eIF4.
c) It doesn't have a 5' MeG, instead it adds a Vpg, and uses an initiation process of the cell called IRES.
What is the mechanism employed by some viruses that allows for the translation of its mRNA instead of the host's?
Viral DNA has no CAP, instead a little protein called Vpg. Instead it uses IRES, which permits the inititation process of the cells (IRES), which permits intitation at an internal methionine
What happens to GTP bound to eIF2
GTP is hydrolyzed to GDP… and the eIF2-GDP is inactive and protein synthesis slows... and it becomes necessary for a special factor to replace GDP with GTP
what is eLF-2B?
the special factor that replaces eIF2-GDP with GTP
With repsect to inactive eIF-2, what does stress (e.g., the lack of Fe, or viruses) cause?
the phosphorylation of eIF2-GDP and blocks reactivation
When do cell need transferin receptors, in high or low iron concentration?
Low Fe
when do cells need ferritin in high or low iron concentration?
high fe
what is ferritin?
an iron storage protein
what do transferrin receptors do?
they transfer iron into red blood cells in order to produce heme
With respect to ferritin RNA, what happens in times of HIGH intracellular [Fe]?
the IRE-BP does not bind to RNA and Ferritin mRNA is translated to make more ferritin
With respect to ferritin RNA, what happens in times of LOW intracellular [Fe]?
the IRE-BP bind mRNA dn prevents translation of ferritin
With respect to transferrin receptor RNA, what happens in times of HIGH intracellular [Fe]?
the IRE-BP does not bind RNA and the transferrin receptor RNA quickly degrades
With respect to transferrin receptor RNA, what happens in times of LOW intracellular [Fe]?
IRE-BP binds the TR mRNA and extends the mRNA lifetime
What is NMD and what are its effects on translation?
Nonsense-Mediated Decay: a nonsense mutation causes a stop codon mid-frame, which is sensed and NMD causes the rapid degradation of the mRNA, which safegards against the production of aberrant proteins
What is RNAi and what is its role?
Interferring RNA, which are RNA that control gene expression by inhibiting translation of mRNA, by causing rapid degradation of mRNA, and by causing modification of chromatin
What is RISC and what is its role?
RNA-induced silencing complex, which takes up RNAi… it recognizes the target mRNA bearing a complementary strand and cleaves it… the RISC is recycled
T/F TGP is a protein that is required for the transcription of most genes.
T/F prokaryotes can acomplish both transcription and translation simultaneously
When is gene express regulated? How does this provide a method for reducing storage needs of DNA
a) during polyadenylation and splicing… b) One gene can code for more than one protein
Can mRNA be modified?
yes, in RNA editin, but it's rare, e.g., to produce different version of apolipoprotein B
Which end of of the DNA strand (5' or 3') contains the sequence that regulation protein lifetime duration?
What is the function of NMD?
Nonsense Medicate Decay identifies and destroys aberrant mRNA
a)What is the function of RNAi b) how is it derived? c) How is this being used clinically?
a) RNAi regulates gene expression at translation or at mRNA degradation… b) RNAi is a ~20 ss nucleotide RNA cut from a larger sequence by 'dicer'… c) it's not but research is being done to find a therapeutic use for it.
If two monozygotic twins demonstrate 100% concordance what type of genetic inheritance is this?
completely genetic
If two dizygotic twins demonstrate 50% concordance, what type of genetic inheritance is this
completely genetic
If concordance is greater among monozygotic twins than dizygotic twins, what does this say about whether or not this is a genetic trait?
there is a component of genetics with the trait
If the concordance for MZ=DZ what type of genetic inheritance is this?
totally environmental
If pyloric stenosis shows concordance for MZ=22% and DZ=2%, is there a significant genetic component?
Which of the following has a genetic component? Cleft lip & palate, pyloric stenosis, schizophrenia, insulin dependent diabetes melitus
What do multiple miscarriages and retardation suggest?
chromosomal abnormalitites
What do earlier age of onset and increasing severity with generation suggest? (anticipation… males)
trinucleotide repeat disease
What is a compound heterozygote?
2 different mutant alleles at the same loci, from mom and dad
If affected individuals are seen in every generation, what does this suggest?
Dominant inheritance
What is the probability of the child of an affected heterozygous parent having an effected child?
What term does the following define? The range of phenotypic expression seen among family members carrying the same mutation.
Variable expressivity
What term does the following define? Individuals carry the disease gene but don not show clinical symptoms (all or none)
Reduced penetrance
What type of inheritance is demonstrated with Marfans?
autosomal dominant with reduced penetrance
What type of inheritance does Huntington's disease demonstrate?
Autosomal dominance/Trinucleotide repeat exansion with age dependent penetrance
If no male to male transmission occurs, what type of inheritance is suggested and the disease is rarely expressed in females? Why is there no male to male inheritance?
X-linked recessive… because males get their X from their mothers… and females get two Xs
What is the chance that the daughter of an affected male of an X-recessive inheritance will be a carrier?
What are the odds that carrier females of an X-linked recessive disease will transmit an allele to their… a) son… b) daughter
both are 50%
If there is an affected in each generation, both males and females are affected, but there are no male to male transmissions and all of the daughters of an affected male are affected, what type of inheritance is suspected?
X-linked dominance
In X-linked dominant, who are more likely to be affected, males or females, why?
Females are 2X as likely to be affected, because they receive an X from mom and an X from dad
What is the probability that an affected male of an X-Linked dominant disorder will have an affected… a) son… b) daughter
a) son - zero… b) daughter 100%
In X-linked dominance inheritance, which gender is more likely to be mildly affected, why?
females, because they have X-inactivation (mosaic), while males can't switch to another X because they have only one X
What is anticiaption and which gender is likely to produce this phenomenon?
a)progressively earlier onset and increasing severity with sucessive generations… b) males
For Huntington's what are the respective penetrance following CAG repeats? <27 CAG… 27-35 CAG… 36-39 CAG… > 39 CAG
<27 CAG: Normal… 27-35 CAG: premutation… 36-39 CAG: reduced penetrance… > 39 CAG: complete penetrance
What is a polymorphism as compared to a mutant allele?
Polymorphism is an allele that exhibits many forms (at least two different types in the population), while a mutant differs from both wild-type and polymorphic alleles (can be used to indicate diseased gene)
What does hemizygous mean?
males having an X and a Y
What is incomplete dominance?
when an intermediate for a trait exists between homozygous and heterozygous phenotypes
What is codominance?
When the phenotype for both alleles is expressed
In sickle cell anemia for a heterozyous individual, what type of inheritance is seen with respect to each allele?
the normal allele is incompletely dominant… the abnormal allele is incompletely recessive… it manifests as a recessive trait
With resect to inheritance, what is it called when half of the normal protein causes disese?
What is it called when the abnormal allele interferes with the function of the normal allele?
Dominant negative effect
What is it called when the mutant allele is enhanced in one or more of its normal properties? Give two examples.
simple gain of function… Huntington's and dwarfing condition achondroplasia
Contrast the following 1) Allelic heterogeneity, 2) locus heterogeneity and, 3) genetic heterogeneity
1) Allelic Heterogeneity is a different mutation at the same loci, 2) locus heterogeneity are mutations at different loci, 3) Genetic Allelic encompasses both heterogeneity and locus heterogeneity
Give two examples of locus heterogeneity.
1) Retinitis pigmentosa (x-linked, autosomal recessive and autosomal dominant forms… and sometimes with retardation) 2) Ehlers-Danlos syndrome [connective tissue collagen being fragile or too elastic] ( x-linked, autosomal recessive and autosomal dominant forms)
T/F Allelic heterogeneity is defined by a mutation at a given locus that results in a clinically indistinguishable or similar disorders.
True, but not completely true… these disorders can also be very different
Give an example of allelic heterogeneity.
Some mutations in the RET gene can cause Hirschsprung disease (colonic motility/severe constipation) or multiple endocrine neoplasia (dominantly inherited cancer) or both
Lecture 9
Which cell type can proliferate (self-renewal) and differentiate into various lineages?
Stem cell
a)Which comes first, the progenitor or a determined cell?… b) what is the difference?
Progenitor --> determined… b) the progenitor has information for identity, but is not stable… the determined cell is now restricted to a cell type but does not yet express the phenotype
Does a determined cell express its phenotype?
As cell lineages develop, when will it usually express terminal markers (phenotype)?
as it differentiate to express terminal markers it will usually coordinate with withdrawl from the cell cycle… which restrict its fate (limit its potential)
What is believed finally happens in differentiation?
a one way street (terminal process) that ends in cell death.
What is special about germ cells?
the completely differentiate, but they retain some potency
What mechanism explains stem cell potency?
repression of differentiation
What is a fate map?
Brings understanding to embryology by tracing cell lineages of daughter cells from a progenitor
How do researchers understand the state of commitment of cell (survive, divide, differentiate or die)?
experimental Transformation, which reveals the processes of determination and induction
What is induction?
cell-to-cell communication (The first critical step in initiating differentiation) that directs cells to new developmental pathways
What is differentiation?
The process of commitment of cells to particular fates
What is a master gene?
the gene that regulates transcription factors expression and drive entire tissue and organ programs in development
Are these master genes well conserved in animals?
yes, thus we can look at worms, flies and frogs
What are the two major mechanisms by which cell identity is established (determination)?
1. Asymmetric Division: Inheritance of cytoplasmic determinant, thus sister cells are born different 2. Symmetric division: sister cells become different due to influences acting on them
Cells are primarily differentiated by which process?
Why are inductive mechanism important?
they are important because they ensure that cells and tissues deveop in the proper spatial arrangement, e.g., axis, limbs, etc.
what is a morphogen
A protein present in embryonic tissues in a concentration gradient that induces a developmental process over a distance… (e.g., the transplantation of a posterior limb bud can induce the new surrounding cells to differentiate with a new game plan)
What is sonic hedgehog?
a diffusible peptide morphogen
How is the morphogen concentration relevant to development?
different cell populations will respond differently with differential gene expression based on this gradient
Do morphogens usually work via passive diffusion?
No, inhibitor of the morphogen help shape the pattern
What are/were hegehog, notch, TGFß, and Wnts considered?
They're now considered inducing reagents… they were once considered peptide growth factors,,, or affectors of the signaling pathways that are regulated by growth factors
what are the 2 types of stem cells?
embryonic and adult
Early in development, which cells layer retains potency and forms the embryo proper and adult tissues, the outer layer (trophecdtoderm) or inner layer (Inner cell mass… ICM) ?
Which cells are totipotent?
What are totipotent (ICM) cells?
Totipotent cells differentiate into embryonic stem cells, which can be used to generate different lineages
Where do embryonic stem cells come from?
How can knock-out or knock-in mouse be made using Embryonic stem cells
inject ES into the ICM of host blastocyte
What is a chimeric mouse?
a mouse that has both the characteristics of its own DNA and the DNA from the contributed embryonic stem cell
Characterize adult stem cells (progentor cell, e.g., myloid).
They are stem cells associated with a particular tissue, like hematopoietic or neural cells
Are adult stem cells identified morphologically?
No, they are identified with cell marker using FACS, where a flourescent marker is added to surface receptor
What is FACS?
flourescence activated cell sorter
What device would you purify a cell population to have only adult stem cells ?
look for cell markers using FACS
How are animal clones made… and why does this confound our understanding of differentiated cell lines?
clones are made with adult differentiated cell nuclei… its confounding only in the sense that in vivo cell don't de-differentiate, but this is offset by the fact that these cells still have their entire genome
What is somatic cell nuclear transfer (SCNT) aka, therapeutic cloning?
an approached used to generate embryonic stem cells to be used to regenerate tissue
How is SCNT accomplished
by taking an embryo and emptying its DNA and replacing it with an adult nucleus --> leading to a nuclear transfer blastocyte… could be used for neuro-degenerative, hamatopoietic and heart disease
T/F: it will not be possible to grow stem cells from adult tissues.
False, it may be possible one day
What is combinatorial control
the use of a discrete number of transcription factor to control a greater number of gene expression