MMG 409 Exam 3 – Flashcards

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Life depends on the ability of cells to grow, copy their genetic information, and ____ pass that information onto the next generation.
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Accurately
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What is the name of the phase that happens when the cell has left the cell cycle?
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G0
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Why are checkpoints in the cell cycle important?
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1. Allows the cell to monitor its own progress
2. Allows the controller to respond to extracellular signals from the environment and from other cells.
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Once the cell is past the checkpoint...
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it cannot pause the cell cycle. The cell is committed to completing the subsequent step.
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What does cdc stand for?
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Cell Division Cycle mutants
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One type of mutant phenotype involves an inactivation of some protein involved in activating or pushing the cell cycle forward. What does that mean?
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That you have basically blocked an activator. Meaning that the cell can no longer proceed through the cell cycle.
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What kinds of mutants divide early, skipping a normal control point?
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Wee mutants
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Wee mutants are expected to be deficient in a product that normally ____ passage through a size checkpoint.
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inhibits
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How do you identify the mutated gene that is responsible for the observed phenotype?
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add back wild type genes, until you find the one that fixes the mutation
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What are the two ways passage through the cell cycle is controlled by?
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Protein phosphorylation (CDKs) and Protein Degradation (Ubiquitin-protein ligases (adding tags))
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The activity of Anaphase-promoting complex (APC/C)is important in pushing the cell through which checkpoint?
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Metaphase Checkpoint
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What is the heart of the cell cycle control system?
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Cyclin-Dependent Kinases (CDKs)
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____ of these kinases (CDKs) rise and fall as the cell progresses through the cycle.
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Activity
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Kinase activity is dependent on presence of ____
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Cyclin
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What are the 3 main classes of cyclins?
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G1, S-phase, and Mitotic cyclins
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Activity of the CDK is regulated by
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1. Cyclin Binding
2. Phosphorylation (2 key ones)
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What greatly increases the affinity for protein substrates?
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phosphorylation
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What is important in control of M-CDK activity, and is caused by the addition of phosphates(2) in the roof of the active site (inhibits activity)?
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Inhibitory Phosphorylation
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What removes inhibitory phosphates like Wee1?
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Cdc25
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CDK activity can be suppressed by?
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The binding of CDK inhibitor proteins(CKIs)
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CKIs are primarily used in controlling ___ and ____ CDKs
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G1 and S-phase
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When a CKI binds to a CDK what does it do?
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Rearranges structure of the CDK active site and holds the CDK inactive until needed
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What are the two distinct enzyme complexes crucial for cell cycle control? And they are both what?
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1. APC/C (Anaphase-promoting complex)
2. SCF (S-phase Controlling Factor)
Ubiquitin Ligases
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Enzyme complexes can tag proteins with ____. Which targets the protein for destruction in the ____.
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Ubiquitin, proteasome
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What is responsible for ubiquitylation and destruction of G1/S-cyclins and certain CKI proteins that control S-phase initiation?
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SCF
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What is important in M-phase. Responsible for ubiquitiylation and proteolysis of M-cyclins and other regulators of mitosis?
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APC/C
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Entry into the M-phase requires this crucial event.
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The activation of Cdc25 which removes the inhibitory phosphate, and the inactivation of Wee1 (kinase)
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Cdc25 is activated by phosphorylation via ___ protien kinase.
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2
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Wee 1 is ____ by phosphorylation.
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inactivated
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What the family of proteins required for normal chromosome segregation?
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SMC proteins (structural maintenance of chromosomes)
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What are the multiprotein complex, overlap with SMC members. ITs phosphorylation is required for condensing activity?
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Condensin
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What holds sister chromatids together?
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Cohesins
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When are cohesions loaded on?
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G1
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In the APC/C what does ubiquitin ligase do?
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Inactivates protein complexes (cohesins) that connect sister chromatids at metaphase
Also degrades the cohesins to permit the onset of anaphase
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Once sister chromatids are separated ____ is activated.
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Cdh1
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Cdh1 is teh specificity factor directs the APC/C to the ___ ___. Cell can begin to ___ mitosis.
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Mitotic cyclins, exit
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G1 is a state of stable CDK ___
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Inactivity
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Where is the function of S-CDK most important?
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in DNA replication
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If a cell in S-phase were fused with a cell in G1....
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the G1 nucleus would immediately enter S-phase, the S-phase nucleus continues DNA replication
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If a cell in S-phase were fused with a cell in G2....
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The G2 nucleus, would stay in G2 , the S-phase nucleus would stay in S-phase
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What are the two sensors in the G2 checkpoint?
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ATM and ATR (kinases)
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How is ATM activated?
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By recognizing double strand breaks
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How is ATR activated?
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By single stranded or unreplicated DNA
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____ are extracellular structures composed of chromatin and granule proteins that bind and kill microorganisms.
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NETs
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What is programmed cell death?
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Apoptosis
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What is cell death following an injury?
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Necrosis
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The presence of phosphatidylserine in the outer leaflet does what?
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1. Helps signal nearby cells and macrophages to phagocytose the apoptotic cell. "Eat Me" signal
2. Blocks inflammation, inhibits the production of inflammation-inducing signals (cytokines) by the phagocytic cell
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Apotpsis depends on an intracellular proteolytic cascade. Which in turn depends on a family of proteases called?
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Caspases
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Caspases are synthesized as ____ precursors which are activated by ____ cleavage.
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inactive, proteolytic
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What cleave and activate other executioner procaspases, as well as specific target proteins in the cells?
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Executioner caspases
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What pathway involves extracellular signals that bind to cell-surface receptors?
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Extrinsic pathway
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What are the 3 domains of the death receptors?
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1. Extracellular ligand-binding domain
2. Single transmembrane domain
3. Intracellular "death" domain
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What has a ligand binding domain but not a death domain. It also competitively inhibits the death receptors?
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Decoy Domain
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What resembles an initiator procaspase, but lacks the proteolytic domain. They also compete with initiator procaspases?
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Intracellular Blocking Proteins (FLIP)
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What is activated in response to injury or other stress, and depends on the mitochondria.
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Intrinsic Pathway
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What family of proteins mediate and regulate mitochondrial outer membrane permeabilization (MOMP) and apoptosis?
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Bcl-2
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What two things are essential for MOMP, and directly cause the membrane disruption?
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Bax and Bak
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What is the only protein that provides the crucial link between apoptotic stimuli and the intrinsic pathway of apoptosis?
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BH3
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What block caspases?
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IAPs (inhibitors of apoptosis proteins0
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As executioner caspases can activate each other (amplification), they must....
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have mechanisms to limit potential "accidental" activation
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Where are IAPs located and what happens when they bind?
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Cytosol, they inhibit any spontaneously activated caspases
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The cancer forming process is called?
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Oncogenesis or tumorigenesis
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Cancer causing mutations usually occur in what?
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somatic cells
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Certain ____ ____ carried in the germ line increase the probability that cancer will occur at some time.
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inherited mutations
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What are the 6 ways tumor cells differ from normal cells?
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1. Drive to proliferate
2. Insensitivity to anitgrowth signals
3. Evasion of apoptosis
4. Tissue invasion
5. Angiogenesis
6. Self-sufficiency in growth signals
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What tumors derive from epithelia? (lung, breast, stomach)
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Carcinomas
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What tumors derive from mesenchymal tissues? (bone, cartilage, fat)
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Sarcomas
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What tumors that start in the cells of the immune system?
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Lymphomas
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Problems with benign tumors arise if their ____ interferes with normal function of if they ____ ____
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size, secrete hormones
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What is the term that describes how tumor cells spread?
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Metastasis
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What is used by cancer cells to penetrate the ECM?
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invadopodium
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Malignant cells usually exhibit the characteristics of?
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Rapidly growing cells
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How do tumors arise from stem cells?
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The cells keep dividing and when a mutation occurs they start to accumulate. Then they could turn into cancer cells
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As more progenitor cells are made from stem cells what trend do they follow?
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As they increase their degree of differentiation, they start to decline in their replication potential.
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What are the 4 ways that cancer can occur as the result of changes in behavior of stem cells?
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1. Niche expansion
2. Niche invasion
3. Niche independence
4. Progenitor self renewal
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Tumors often arise at sites of ____ or ____
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Injury or infection
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Whats expression is induced by low oxygen?
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VEGF
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What induces transcription of VEGF and is activated by low oxygen?
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HIF-1
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What is the term to describe the time when cells can no longer divide?
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senescence
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Is APC a proto-oncogene or tumor suppressor?
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Tumor suppressor because you need a loss of function to get the mutant phenotype
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When DNA is damaged what prevents the cell from going from G1 to S phase?
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p53
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Activation of p53 can lead to ____
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Apoptosis
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What are the 4 ways a proto-oncogene gets converted to a oncogene.
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1. Mutation
2. Amplification
3. Chromosomal translocation (fusion making a chimeric protein)
4. Chromosomal translocation (expression by a different promoter that causes misexpression)
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What is a dominant oncogene where the glycine at position 12 changed to another amino acid?
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Ras
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Ras reduces its GTPas activity and keeps in in the ___ GTP bound state.
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active
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What promotes cell survival or proliferation, has dominant mutations, arise from point mutations, and cause a gain of function that allows for unregulated cell proliferation and survival?
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proto-oncogenes
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What normally inhibits cell survival and proliferation, mutations are recessive, arises from deletions and point mutations, and causes a loss of function that allows unregulated cell proliferation and survival?
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Tumor-suppressor genes
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What normally repairs are prevents DNA damage, mutations are recessive, arises by deletion and point mutations, and causes a loss of function that allows mutations to accumulate?
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Caretaker genes
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What when mutated allows for the degradation of beta-catenin and thus leads to the activation of proto-oncogenes?
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APC
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What represses ras?
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NF-1
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What activates ras?
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Sar and Abl
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How does ras cause lead to and increase in cancer?
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It reduces the GTPase activity and keeps it in the active GTP bound state.
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What adds OH groups to molecules that turns normally harmless molecules to cause damage to DNA?
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Cytochrome P-450
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What forms when amino acids and creatine react at high temperatures?
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Heterocyclic amines (HCAs) which are carcinogens
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What disease causes a disruption in nucleotide repair, which means DNA repair stops functioning properly?
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XP
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