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Cell Bio Final Exam

Terms in this set (76)

What is the structure and function of the nuclear lamina?
Meshwork of intermediate filaments, provides structural support for the nucleus. It resists bending and stretching. Tethers the membrane components and mediates interactions between the inner and outer nucleus.
What role does prenylation serve in the assembly of the nuclear lamina?
Targets lamins to the inner nuclear membrane. The addition of hydrophobic molecules to a protein or chemical compound. Carbon-group is covalently attached to the C-terminal Cysteine. Lamins A and C are cleaved off after protein incorporation into the nuclear lamina. Lamins B is not cleaved off.
How does the nuclear lamina enable the nucleus to communicate with both the cytoskeleton and the extracellular matrix?
The laminas reach the inner nuclear membrane with the help of the prenyl groups, they are deprenylated and left on the inner nuclear membrane with their associated proteins. They can reach out of the cytoplasm and interact with things like actin and myosin (major components of the ECM and cytoplasm) and then nucleus interactions can communicate through the laminas and the associated proteins.
How might the nuclear laminas influence gene expression?
With which groups are prenylated and if they are or are not prenylated when they are supposed to be would alter the expression. Also, mutations that alter mRNA splicing could result in deletions like in Hutchinson Gilford Progeria Syndrome.
How is specificity and directionality of transport through the NPC determined?
It's dependent on the signal of the cargo molecule that is being transported. The transport signals are the NLS or the nuclear localizing signals and the NES or nuclear export signals.
The fate of the ________ during mitosis is...
-nuclear lamina
-nuclear pore complex
-nuclear envelope
How is the nucleus of a human cell reassembled following mitosis?
-nuclear lamina: phosphorylated by Cdc2 and other kinases, this results in the dissociation of the lamina into lamin dimers. Lamins A and C are prenylatrd, Lamins B is unprenylated.
-NPC: breaks apart
-nuclear envelope: the envelope fragments off and the vesicles fuse with the endoplasmic reticulum. The lamins become phosphorylated, the nuclear envelope fragments, the lamins become dephosphorylated, the nuclear envelope fragments become fused, the fusion then envelopes the chromosomes.
Describe the function and composition of the nucleolus.
Primary function is to assemble ribosomes. The nuclear organizing center which holds the genes for pre-rRNA are found within the nucleolus. This structure disassembles at the beginning of mitosis and reassembles during telophase.
What would be the consequence of the specific inhibition of RNA polymerase I on nuclear structure?
Ribosome assembly would not begin because it starts with transcription of pre-rRNA by polymerase I.
How is DNA packaged within the interphase nucleus?
Histones wrap around the DNA bound fragments. Composed of H2A, H2B, H3, and H4 with an internucleosomal DNA bound by H1. The "histone amino terminal tail" determines the translation because of the "histone code" (writers for the patterns, read by effector proteins).
What are the characteristics of euchromaitn and heterochromatin?
Euchromatin: are expressed, associated with the NPC
Heterochromatin: condensed to the point of not being expressed, they are associated with the nuclear envelope EXCEPT the NPC.
How do human germ cells differ from somatic cells in their DNA packaging?
Human sperm cells are too small to accommodate the DNA packaged with nucleosomes, so the spermatid strip off the nucleosomes and package to protamines which neutralize the negative charge and wrap around the helix to be packaged. Not a lot of gene expression occurs, so they can be condensed.
What is the primary function of the FG repeat proteins of the NPC?
Serves as a binding site for the nuclear transport receptors, importins/exportins. They function to block non-specific movement of macromolecules through the NPC because whatever comes into the cell. They act as aqueous channels with hydrophobic conditions.
How is energy used in nuclear transport? (import)
Once the cargo is in the nucleus, Ran-GTP binds and causes a conformational change in the importin which releases the cargo in the nucleus, one the cargo is released the importin and the Ran-GTP leave the cell where the Ran-GAP induces hydrolysis (removal of phosphate) of GTP-->GDP. The Ran-GDP then returns to the nucleus side of the membrane and interacts with the GEF which results in an exchange of GDP-->GTP to be used again. Ran-GTP dissociates importins and cargo.
How is energy used in nuclear transport? (export)`
The cargo binds to the exportin because of the Ran-GTP where it then goes through the NPC. It then goes through the GAP where it goes from GTP-->GDP; this exchange causes the cargo to be released. Once the cargo is released, the Ran-GDP goes back into the nucleus side of the membrane to interact with the GEF. Ran-GTP is required for exportins to bind to cargo.
Why is the specific localizationof Ran-GDP and Ran-GEF essential for nuclear transport?
GEF is located on the inside of the nucleus because the interaction with the importin causes the release of cargo and the interaction with the exportin causes the binding of cargo.
How might the regulation of nuclear transport contribute to the control of gene expression in response to extracellular signals?
When a signal comes in and something along the lines of a transcription factor, important protein, or something else comes into the nucleus via nuclear transport the new gene can be transcribed and expressed.
Why is the nucleus a highly dynamic structure that responds to the environment?
The cell needs to be able to respond to signals for cell division, or the nucleus with the creation of proteins. If not, the cell would not be able to function properly.
Why is RNA processing necessary for the synthesis of 28S, 16S, and 5.8S ribosomal RNA?
This is the transcribed part of the RNA. It becomes specialized proteins and a part of the 60S ribosomal subunit.
Why might alpha and beta globin result in co-localization?
Through co-localization, genes are able to end up in the same place at the same time in preparation for cell division. They become spatially juxtaposed with the nucleus.
What is the relationship between the nuclear envelope and the endoplasmic reticulum?
The outer membrane is touching the endoplasmic reticulum.
The human genome contains ~20,000 genes that together encode for >100,000 unique proteins. What is the primary mechanism?
Alternative mRNA splicing; regulated process during gene expression that results in a single gene encoding for multiple proteins.
What are the major types of sequence elements that comprise ~98.8% of the human genome?
Introns and regulatory sequences (24%)
Unique, non-coding DNA (15%)
Repetitive DNA unrelated to transposable elements(15%)
Repetative DNA including transposable elements and related sequences (44%)
Transposable elements: DNA sequences capable of moving within the genome.
What are the differences between the human genome and that of E.coli?
Humans have larger genome size, number of genes and have a smaller percentage of protein-coding sequences.
How does the human nuclear genome differ from the human mitochondrial genome?
Mitochondrial DNA is composed of single, double stranded circular molecules. No histones or proteins associated with mitochondrial DNA. mDNA contains no introns because it is in a highly environment with a much higher rate of mutation than nuclear DNA. mDNA is only inherited from the mother, mDNA codes for mitochondrial ribosomes and transfer RNA.
What advantage has globin gene duplication provided to humans?
New functions, like tissue specific expression, developmental regulation, altered enzymatic activity. Ex. Human fetal globin genes; fetal proteins possess a higher affinity for oxygen than adult globin proteins.
What are the enzymatic activities of LINE and HERV?
Reverse transcription; an enzyme used to generate complementary DNA from an RNA template
Integration; successful binding of foreign DNA into an organisms own.
What are the key structural differences that distinguish LINE from HERV?
LINE; long interspersed elements, may encode reverse transcriptase and a DNA endonuclease (enzymes that cleave the phosphodiester bond within a polypeptide chain)/integrase. One end has a direct repeat bp, the other has a poly-a tail.
HERV; human endogenous retrovirus, have direct repeat and poly-a tail, but an LTR (long terminal repeat).
Why are all transposable elements flanked by direct repeats?
The 5' flanking region is often an untranslated region of DNA which isn't transcribed into RNA. It's transcribed into mRNA, but it is immediately removed and isn't included in the matured RNA.
Why are telomeres essential?
They solve the problem of replicating the end of the lagging strand which if it weren't for telomeres would be much shorter than the leading strand. They support indefinite proliferation.
How does transposase function in the movement of DNA transposons within the genome?
They function in the movement of DNA transposons within the genome by the DNA endonuclease recognizing the inverted repeats at the ends of the transpons and cleaving them from the genome. Make staggered cuts in the target DNA allowing for insertion. Cut and paste mechanism.
How might SINE elements enable humans to breed animals drastically different like Dachshunds and Great Danes?
SINE elements are retrotransposable elements so they contribute to the overall pasticity of the genome. Enzymes required:
1)RNA polymerase II
2)Reverse transcriptase
3) Integrase
4) Host cell DNA repair machinery
What features would a retrotransposable gene need to acquire in order to be expressed as mRNA?
1) Long term repeats (LTR)
2) Complete, or partial gene structure
3) short flanking, direct repeats of host DNA sequences at the site of integration
To be expressed as mRNA the retrotransposable gene would need to have a promotor-most aren't expressed because they don't contain a promotor.
What roles might junk sequences have played during the evolution of the human genome?
They are transposable elements so if a new sequence is inserted into the genome, there is going to be genetic change which may (if beneficial) be selected for which would lead to evolution. Genetic variation is a pre-req for evolution.
What is meant by the term "histone code"?
The different combinations of histone modifications that are read by nuclear proteins that modulate gene expression.
What insight has FISH (fluorescence in situ hybridization) provided into the organization of the eukaryotic nucleus?
Provides visuals of direct and localized specific DNA sequences during different phases of the cell cycle.
What is "chromosome territory"?
The area of the nucleus where the chromosomes reside.
What is the primary goal of the field of pharmacogenetics?
To study how genetic differences in multiple genes influence the variability of drug responses. It is all determined by an individual's genetic profile.
What are two types of epigenetic modifications and what is their effect on the expression of the genome? How can they play a role in the development of cancer?
DNA methylation (5-methylcytosine; methyl group displayed in the DNA major groove where it is accessible to regulatory proteins) and Histone modification (metylation, acetylation, ubiquitination, sumolation, phosphorylation). Epigenetic modifications can repress or promote gene expression depending on what the modification is. They contribute to the dynamic nature of the genome. Epigenetics can affect the expression of genes and how/when they are turned on/off, if there is a negative mutation in the gene expression where a normal gene is const. on, then there could be an overexpression of the gene causing over-proliferation.
What is meant by "genomic imprinting"? Why might it have evolved in mammals?
Parent-specific epigenetic modifications of the germline. This means there's different modifications within the male/female germlines. These modifications appear to be unique in each mammal. The non-mendelian form of inheritance might have evolved in mammals because the genetic traits passed down are favorable.
What is required for somatic cell evolution?
Selective pressures; nutrients, O2, immune cells, waste products, growth/survival signals, drugs. Ex. Dolly the sheep; the nucleus of the cytoplasmic (egg) donor and the mammary cell of the nuclear donor. They are combined and put into a surrogate. Once the blastocyst develops; a new, cloned individual is born-clone of the nuclear donor.
Therapeutic vs. Reproductive cloning.
Therapeutic- production of cells or tissues for therapeutic use and treatments.
Reproductive- the production of an entirely new organism
Why are most human cancers derived from epithelial cells?
They come in contact with the most carcinogens compared to non-epithelial cells. Also, epithelial cells are always proliferating which gives them a higher chance of metastasis.
What are some of the obstacles that normal cells encounter on their way to becoming a metastatic cancer cell?
Most cells only proliferate until a certain point and then arrest and stay in the G0 stage of the cell cycle. Also, the presence or the absence of growth factors.
Why are the peaks per capita for cigarette consumption and lung cancer deaths offset by ~25 years?
There have been anti-smoking campaigns which is the least of it, but also smoking a cigarette once doesn't give you cancer; the cancerous cells become built up through the carcinogens in the cigarette.
What are the basic characteristics for...
-proto-oncogenes
-oncogenes
-tumor suppressor genes
-Proto-oncogenes; normal cells that have the potential to convert to an oncogene
-Oncogene; gain of function mutations, dominant, non-inheritable. They are genes that promote cell growth
-Tumor suppressor genes; functions lost in cancer cells, inability to control cell growth. They are recessive and inheritable.
How might proto-oncogenes, oncogenes and tumor suppressor genes impact proliferation? Which might contribute to inherited predispositions to cancer?
-Proto-oncogenes; can trigger a stop in the cell cycle
-Oncogenes; can cause the cell cycle to continue when it shouldn't
-Tumor suppressor genes; can stop the cell cycle-->these genes may contribute to an inherited pre-disposition to cancers.
Why should tumors be viewed as complex tissues or 'organs'?
Normal somatic cells do not contain the same characteristics as cancer cells. Tumors consist of both cancer cells and normal cells, they envelop normal cells making them become part of the tumor; they interact.
What is meant by 'heterotypic signaling'?
Communication between dissimilar cell types that is used to encourage proliferation. This allows for representation of each cell type in tissues. This causes cancer cells to induce normal cells to provide essential growth factors.
How do traditional 'anti-cancer' drugs work?
They use agents that are not only toxic to cancer cells, but normal cells as well. They damage the DNA or inhibit DNA replication.
How do targeted anti-cancer drugs differ from traditional chemotherapies?
Targeted treatments block the activity of specific oncogenes that drive the tumor growth- i.e; Avastin, Herceptin
Approximately 50% of human tumors are found to have inactivating mutations in p53, why?
P53 inactivation is the most common mechanism for evasion of apoptosis in human tumors with damaged DNA. Because they don't go through apoptosis, they proliferate with damaged DNA and produce more cancer cells.
How do tumor promotors contribute to the development of cancer and how is this process distinct from the role of carcinogens in the initiation of cancer?
They promote the proliferation of cells, some of which contain damaged DNA. Because of this, tumor promotors expand the population of normal and mutant cells. The increased population increases the probability of a tumor forming. Carcinogens induce genetic change within the genes themselves rather than promoting cell proliferation. Tumor development in this case is dependent on dose and the time exposure to the carcinogens.
How do viruses like human papilloma virus (HPV) contribute to the development of cancer?
HPV induces cell division by inactivating the tumor suppressor protein, Rb. They also encode to inactivate p53. This inactivation results in the release of the active transcription factor E2F which is required for the activation of genes that encode components of DNA replication machinery as well as genes that encode proteins required for entry into S phase.
Why does HPV encode proteins that inactivate both Rb and p53?
The inactivation of these genes results in a prolonged cell cycle instead of being cut short by going through apoptosis.
What types of mutations (inactivating/activating) and epigenetic changes would you expect to find in...
-oncogenes
-tumor suppressor genes
in cancer cells?
-Oncogenes; gain of function mutations (overactivity), normal cells--> single mutation event, creates oncogenes--> activating mutation enables the oncogene to promote cell transformation
-Tumor suppressor genes; loss of function (underactivity), normal cells-->mutation event, inactivates tumor suppressor gene-->no effect of mutation in gene copy--> second mutation event, inactivates second gene copy--> two inactivating mutations functionally eliminate the tumor suppressor genes promoting cell transformation
Why does drug resistance often develop in response to both targeted and traditional chemotherapies?
Most treatments are introducing a new selective pressure to the cancer cells, which usually causes them to spread, move or evolve.
How might cancer cells develop drug resistance?
Chemotherapies kill drug-sensitive cells and leaves a higher proportion of drug-resistant cells. When the tumor grows again, the remaining tumor cells are thee drug-resistant cells which is why chemotherapy may fail.
Why do most human cells not express telomerase?
Somatic cells don't need it to divide. Each time there is replication, the strands get shorter and at some point the cell, instead of dividing, will just arrest and become a cell in G0.
Why was angiogenesis initially assumed to be an ideal anti-cancer drug target? Why is it flawed?
It was assumed that cancer therapies that target normal cells wouldn't be subject to the development of resistance. Angiogenesis is new blood vessels forming from pre-existing blood vessels to feed tumors. It's flawed because it slows the progression of metastatic tumors, but didn't improve the quality of life. It causes adverse effects like blood clotting because of the increased pressure on the vessel. If the capillaries don't form, they have to get less oxygen and blood--> cancer cells are able to leave (selecting for metastatic cells)--> potential outcome of using drugs like this
How does diet influence the phenotypes of queen and worker honeybees
"Royal jelly" or Dnmt3 silences key genes which encode for enzymes involved in genome wide gene silencing. When Dnmt3 is active in bee larvae, the queen genes are epigenetically silenced and the larvae develop into the default "worker" variety. But when royal jelly turns Dnmt3 off, certain genes jump into action that turn the lucky larvae into queens. The queen develops functional ovaries and a larger abdomen for egg laying, the workers remain sterile.
Why are most calico cats female?
The gene for black coat is on one X gene while the gene for orange coat is on another gene. Random x chromosomes are silenced by DNA methylation and chromatin modifications into barr bodies. When one of the x chromosomes is silenced the one color (black or orange) is expressed. Because female's genotypes are XX and males are XY, if one x is inactivated, there is still another. For males, calico cats are feminized males (XXY) because they have an x to be silenced. Daughter cells inherit active or inactive X chromosomes, creating a cat with patches of coat color
Genomic Imprinting
Established at two distinct phases in development; gametogenesis (imprint marks on maternal/paternal chromosomes erased, followed by establishment of primary imprints-->reflected in sex of idividual) and after fertilization (global demethylation events occur in zygote, first in paternal then maternal, remethylation of diploid). Certain genes are expressed in a parent-of-origin-specific manner. If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed.
Paternal conflict hypothesis
Also known as "kinship theory of genomic imprinting". There's an inequality between the father's genes (that encode for greater fitness) at the expense of the mother's genes. Mother's genes tend to be growth limiting where the father's are growth promoting.
Tumor types
Benign; confined, resemble normal cells, can be removed
Malignant; capable of invading tissues, can spread throughout the body
Tumor classification
Carcinoma; epithelial, more likely to be exposed to carcinogens, already high proliferation rate
Sarcoma; solid in connective tissue (rare in humans)
Leukemia/Lymphoma; blood/immune
Aneuploidy
An abnormal number of chromosomes is a common occurrence in tumors, along with deletions, duplications and translocations
Aflatoxin
Mycotoxin produced by fungus that damage DNA (metabolic activation). Infection of permissive cells (virus is able to circumvent host defenses and is able to replicate) results in lysis, cell death= no tumor development. In non-permissive cells (a cell that doesn't support virus replication) viral DNA may remain in cells where it may encode proteins that contribute to tumor development.
SV40
Same as HPV-induce cell division by inactivating the tumor suppressor protein Rb. These viruses also encode proteins to inactivate the tumor suppressor p53. Inactivation of Rb results in the release of the active transcription factor E2F, which is required for the activation of genes that encode components of the DNA replication machinery, as well as genes that encode proteins that are required for entry into S phase.
Self-sufficiency of growth signals
-Alteration of extracellular growth signals
-Autocrine stimulation
-Alteration of transmembrane receptors
Ex; HER2, overexpression of protein, dimerize without ligand, promotes signaling
Goals of anti-cancer drugs
Damage the DNA
Block DNA replication
Block mitosis, specifically cytokenisis
Major categories of chemotherapy drugs
-dNTP synthesis blockers: methotrexate, fluorouracil, hydroxyurea, mercaptopurine
-DNA damaging: cisplatin, danorubicin, doxorubicin, etoposide
-Mitotic spindle disruptors: vinblastine, vincristine, paclitaxel
Hallmarks of cancer
1) Self-sufficiency of growth signals
2) Insensitivity to anti-growth signals
3) Evasion of apoptosis
4) Limitless replication potential
5) Sustained angiogenesis
6) Invasion and metastasis
Cajal bodies
Potential site of snRNP assembly
Nuclear speckles
Potential storage site for mRNA splicing factors.
DSCAM-down syndrome cell adhesion molecule
Functions as an identifier by alternatively splicing cassette exon clusters.
Histone modifications
-methylation; methyl groups are transferred to amino acids, can increase or decrease transcription
-acetylation; an acetyl functional group is transferred from one molecule to another
-ubiquitination; ubiquitin is attached for destruction
-sumoylation; nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle.
-phosphorylation; addition of a phosphate group
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