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Faculty of Medicine Department of Cancer Research and Molecular Medicine

Exam MOL3000 Introduction to Molecular Medicine

Friday December 5th 2008, 9.00 am - 1.00 pm

ECTS credits: 7.5 Number of pages (included front-page and MCQ answers sheets): ………………………….

Contact person during the exam: Marit Otterlei, 92889422

Exam results: 5th January 2009 Examination results are announced on http://studweb.ntnu.no/

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Answer: Domain structure of the LDL receptor LDL-receptor is a transmembranal protein : Sequential steps in LDL receptor pathway: Receptor mediated endocytosis If intracellular cholesterol is low. Defective LDL-receptor results in hypercholesterolemia Tendon Xanthomas 2 . (5p) b) Explain how inactivating mutations in the LDL receptor contribute to the clinical and biochemical phenotype resulting in cardiovascular disease (5p). localisation regulation and function of the LDLreceptor. more cholesterol is synthesized If LDL-receptor is defective.Question 1 (10p) a) Describe the structure. cholesterol is synthesized in abundance HMG-CoA reductase is the regulatory enzyme in cholesterol biosynthesis Cholesterol lowering drugs of the type “statins” inhibit HMG-CoA-reductase THE LDL receptor is required for LDL uptake in cells.

Five classes of LDL receptor mutations Question 2 (10p) In eukaryotic cells the regulatory regions of genes contain short stretches of DNA which serve as binding sites for proteins that regulate gene expression. TFIIB. har enzymatisk aktivitet. The proteins that bind to these sites are termed transcription factors. Bare en av faktorene. Answer: Spesielle transkripsjonsfaktorer (aktivatorer) gjenkjenner og binder til korte DNA sekvenser i genenes proximale og distale promoter. TFIIF. leucin-zipper. Spesielle transkripsjonsfaktorer kan inndeles i familier eller klasser basert på struktur.a. Answer: De generelle transkripsjonsfaktorene utgjør et sett på minst fem proteiner som er nødvendig for at RNA polymerase II (RNA pol II) skal gjenkjenne og binde korrekt til genets promoter. De spesielle transkripsjonsfaktorene er sentrale i rekruttering av transkripsjonsmaskineriet (RNA polymerase og de generelle transkripsjonsfaktorene) til genets core-promoter. Faktorene betegnes TFIID. og TFIIH. bl. en kinaseaktivitet som er rettet mot den C-terminale ”halen” til RNA polymerasen og som er viktig i selve initieringen. 3 . TFIIE. og dette er deres overordnede funksjon i cella. proteinkodende gener. which functionally can be divided into two classes: “basal transcription factors” and “special transcription factors (activators/repressors)”. og kanskje alle. De generelle faktorene assosierer med RNA pol II og besørger korrekt plassering i forhold til startpunktet for transkripsjon. og helix-loop-helix proteiner. Man antar at disse faktorene er nødvendig av transkripsjon av de fleste. What are the functional roles of “basal transcription factors” and “special transcription factors (activators/repressors)” in the cell? Explain the main functional difference between these two classes of transcription factors. De binder vanligvis som dimerer og kan være sammensatt av to identiske subenheter (homodimerer) eller to ulike subenheter (heterodeimerer). Eksempler er zink-finger proteiner. TFIIH.

muskel og fettvev. a programming language that can be used to automate various tasks. Dersom man gjentar dette iterativt har man en PSI-Blast lignende prosess. Answer: Denne oppgaven tester forståelsen av hvordan PSI-Blast fungerer. basert på multippel alignment. but unfortunately you do not have access to PSI-Blast. Bindningen fører til autofosforylering av reseptoren hvilket via forskjellige kinasereaksjoner fører til aktivering av en rekke signalkjeder intracellulært. you do have access to Pro-Blast. 4 . Insulin har effekter på fettsyremetabolism og hemmer lipolyse. which can do a Blast search with a user-specified profile. Question 4 (10p) Describe the main actions of insulin Answer: Insulin hemmer glykogenolyse og glukoneogenese i leveren.Question 3 (5p) You want to do an iterative PSI-Blast search. Explain how you will combine this with ClustalW to make a PSI-Blast like tool. bruke ClustalW til å lage et multippelt alignment av disse. You also have access to Perl. Insulin hemmes også opptak av glucose i lever. Why are these genes often involved in tumor development from hematopoietic cells? Answer: Gener for immunglobulin og T-celle reseptorer Eksempler: Neseten alle former for leukemier og lymfomer og myelomatose Pga. omforme dette til en profil. Question 5 (5p) Many of the cancers that originate from hematopoietic cells have translocations involving genes that participate in immune defence reactions. Essensen er at PSI-Blast bruker søkeresultatet til å lage en profil. og så søker med den profilen i neste iterasjon. However. Insulin er et anabolt hormon. at disse genene gir opphav til spesifisitet i immunforsvaret som medieres ved hematopoetiske celler gjennom prosesser som omfatter kutting og ligering av DNA. og bruke den som input til Pro-Blast. Give examples of such genes and cancers. Dette blir så gjentatt med oppdatering av profilen for hver iterasjon. like reading and writing protein sequences and run software tools. Dette kan man etterligne ved å bruke Perl til å hente ut sekvensene fra siste søkeresultat. Insulineffektene formiddles gjennom binding til insulinreseptorer i cellemembranen. Mangel på insulin gir hyperglykemi og forhøyede nivåer av fettsyer i blodet. basert på siste søkeresultat. Insulin har effekter på proteinsyntes gjennom å øke opptak av aminsosyrer i forskjellige vev og øke syntes av proteiner.

Det siste øker mulighetene for feil-ligering av DNA som kan medføre aktivering av onkogener. 5 .

DNA and proteins can be separated by size by gel-electrophoresis. Which protein is this? A c-myc B gp120 C Ras D p53 E hsp70 Corrects answer: D 3. In the G1-S phase of the cell cycle the cells are checking the environment. Many proteins are capable of detecting DNA damage and lead to cell cycle arrest. The cell cycle is divided into several phases and different biochemical event are characteristic of the different phases. Latent / resting viruses do not produce much protein and can be hard to diagnose. each question 1p. Answer the questions on separate MCQ answers sheets enclosed. 1. Only one cross for each question (the best alternative). growth conditions and presence of DNA damage. one protein is more important than others. One answer is the most correct. thus SDS is making the aggregates easy to detect D SDS preserves the enzyme activity of the proteins Corrects answer: A 4. Why do we use SDS (sodium dodecylsulfate) in gel-electrophoresis? A SDS denaturates the proteins. In which phase is the DNA duplicated / copied ? A S-phase B M-phase C G0-phase D G1-phase E G2-phase Corrects answer: A 2. unfolds them and gives them an uniform charge B SDS is emitting light when it is bound to proteins C SDS leads to protein aggregates.MCQ. Which techniques could be used in order to detect latent virus? 6 . This is also a tumor suppressor gene.

What is the correct designation of these nucleotide fragments? A Okazaki fragments B RNA primers C Primases D Telomers E Centromers Corrects answer: B 8. DNA replication initiates at specific chromosomal sites. 7 . These sites are termed: A Okazaki fragments B Replication forks C Replication primers D Replication origins E Replication bubbles Corrects answer: D 7. This region is successive shortened during mitosis. iso-electric focusing and western blotting Corrects answer: B 5. Eukaryotic cells contain different RNA polymerases. What do we call these regions on the chromosomes? A Kinetochores B Telomers C Haplotypes D Centromers Corrects answer: B 6. A DNA polymerase cannot initiate DNA replication on its own but rely on the presence of short nucleotide fragments. At each end of all chromosomes there are a few kilobases of DNA that contain a specific 6bp repeated sequence. which transcribe different sets (types) of genes.A SDS-polyacrylamid gelelectrophoresis B Polymerase chain reaction (PCR) and DNA gelelectrophoresis C Polymerase chain reaction (PCR) and iso-electric focusing D 2D-gelelectrophoresis.

endonucleaseactivity C 5’. Many DNA polymerases have the possibility to remove mis-incorporated nucelotides during DNA-replication. What do we call this proof reading activity of the polymerases? A 5’.5’.exsonucleaseactivity D 3’.exsonucleaseactivity E Topoisomeraseactivity Corrects answer: D 8 .endonucleaseactivity B 3’.5’.3’. In eukaryotic cells approximately 180-200 base pairs of DNA is twisted around an octamer of basic proteins. What is the correct term of this octamer? A Histone B Chromatin C Chromosome D Nucleosome E Chromatid Corrects answer: D 10. In human cells methylation occurs usually on Cytosine (C) in the context of: A 5’-CpA-3’ B 5’-GpC-3’ C 5’-CpT-3’ D 5’-CpG-3’ E 5’-ApC-3’ Corrects answer: D 11.3’. DNA methylation is a modification of one of the DNA’s four bases.Which polymerase transcribes the protein coding genes? A RNA polymerase I B RNA polymerase II C RNA polymerase III Corrects answer: B 9.

Gluconeogenesis is the body`s own synthesis of glucose. Which organ is the main site for gluconeogenesis? A Liver B Brain C Kidney D Milt E Pancreas Corrects answer: A 14. but not for brain stroke. your body breaks down fatty acids via beta-oxydation. They showed this by growing cells for a long period of time with “heavy” isotop of nitrogen. e.g. When you fast. High blood pressure (BP) is one such risk factor Which statement is the more correct one among those below? A High BP is a risk factor for coronary heart disease.”heavy”. Which forms of DNA (”light”. When they isolated the DNA from these cells at different time point they found combinations of “light” and “heavy” as well as “hybrid” DNA.or ”hybrid”) did Meselson and Stahl find after incubation in ”light” nitrogen for 2 cell generations? A Only ”light” DNA B Only ”heavy” DNA C Equal amount ”light” DNA and ”hybrid”-DNA D Equal amount of ”heavy” DNA and ”hybrid”-DNA E Equal amount ”light” DNA and ”heavy“ DNA Corrects answer: C 13. followed by culturing for a specific number of generations in “light” isotop of nitrogen. the brain. it fills up during “good times” and is used during “bad” times. Meselson and Stahls experiment from 1958 demonstrated that DNA is replicated in a semi-conservative manner. The body have a storage of energy. Several risk factors for cardiovascular disease (CVD) have been identified. Where in the cells do we have beta-oxydation? A Endoplasmic reticulum B Cytosol C Mitochondria D The Golgi-apparatus Corrects answer: C 15.12. Many organs are dependent of glucose from the blood as the main energy source. 9 .

D CVD is a major cause of disease in men. Cardiovascular disease is an important cause of death. B CVD is a leading cause death only in the western world and Japan. How does this drug induce relaxation of the blood vessels? A By degradation to the signalling molecule nitric oxide (NO) B By activation of the enzyme nitric oxide (NO) synthase C By inhibiting the enzyme nitric oxide (NO) synthase D By activation of protein kinase G Corrects answer: A 19. Corrects answer: B 16. 10 .B High BP is a risk factor for coronary heart disease and brain stroke. but not in women. Corrects answer: A 17. Pathologic changes in the production of neurotransmitters may lead to hypo or hyper function of the extracellular signalling system. C High BP is mainly a risk factor for cardiovascular disease in elderly persons. Which of the following statements about cardiovascular disease (CVD) is most correct? A CVD is a leading cause of death world wide. The drug leads to expansion (relaxation) of blood vessels and increased supply of blood and oxygen to the heart. Nitroglycerin is a medication used for treatment of angina pectoris. Which is the best definition of extracellular signalling molecules? A Different proteins which regulate the function of other cells B Very small molecules which are transported via blood vessels C All molecules released from a cell and which are able to induce response in another cell D A specific hormone for intracellular communication E All molecules necessary for growth in different tissues Corrects answer: C 18. D High BP is a risk factor for CVD. but is now surpassed by cancer. but with regional differences. C CVD was a leading cause of death world wide. Extracellular communication is often considered as biochemical signalling between cells. but not an independent risk factor.

The HFE protein acts by binding to: A Hepcidin and inhibit the iron uptake B Beta-2-microglobulin and increases the secretion of iron C Beta-2-microglobulin and inhibit the iron uptake D Ferroportin and inhibit the iron uptake E Ferroportin increases the secretion of iron Corrects answer: C 21. What would be the physiological effect of this? A No activation of adenylyl cyclase B Increased association with the β and γ subunits C Inhibition of β and γ complex formation D Increased activation of adenylyl cyclase and increased cAMP-mediated signalling E Decreased activation of adenylyl cyclase and decreased cAMP-mediated signalling Corrects answer: D 11 . while Gαi isoform inhibits adenylyl cyclase. β and γ subunits. Trimeric G-proteins consist of α. Gαs isoform stimulates. The most common form of haemochromatosis among Caucasians is caused by mutation in the HFE gene. Presume that you have isolated a mutant of Gαs with decreased hydolysis of GTP.What kind of disease listed below is caused by loss of dopamine? A Huntington’s disease B Neuropathy C Parkinson’s disease D Multiple sclerosis (MS) Corrects answer: C 20. The Gα subunit is a GTPase switch protein that cycle between active and inactive states.

22. Cancers often involve mutation in several proteins participating in intracellular signalling and transcriptional regulation. Assume that a somatic mutation has arisen in the protein c-Ras. The function of Rb is most precisely described as: A Inhibits transcription by phosphorylation of E2F B Inhibits transcription by binding to E2F C Inhibits transcription by activation of cyclin D D Is a protoonkogen which activates the transcription by binding to E2F E Binds E2F and P16 kinase and subsequently activates transcription Corrects answer: B 23. and calsium plays an important role in this process The molecular signalling mechanisms involved in this process involves the following process: A ATP-dependent activation of Ca2+ channels B IP3-gated release of Ca2+ from endoplasmatic reticulum (ER) C Voltage-independent Ca2+ channels D Ca2+-mediated endocytosis 12 . The BRCA1 protein is: A A growth factor B A tumour suppressor protein C Involved in inhibition of estrogen-independent intracellular signalling D Involved in DNA repair E A kinase crucial in estrogen receptor-mediated signalling Corrects answer: D 24. Individuals with mutations in BRCA1 and BRCA2 genes are predisposed to develop breast and ovarian cancer during lifetime. What could be the consequences of such a mutation? A Activation of tumour suppressor proteins B Constitutive activation of signalling pathways C Inhibition of tyrosine phosphorylation D Cell cycle arrest Corrects answer: B 25. The protein Rb plays a crucial role in cell cycle regulation. Insulin is secreted from β-cells in pancreas in response to increased blood glucose level.

Which of the following alternatives constitutes an important difference between these forms? A Blood glucose is higher in type1 than in type 2 diabetes B Antibodies against pancreatic islet tissue are found in type 1 but not in type 2 diabetes C Type 1 diabetes is always treated with insulin. Proinsulin is later divided into insulin and C-peptid Corrects answer: A 29. type 2 diabetes more common in men Corrects answer: B 28. type 2 diabetes never D Type 1 diabetes is more common in females. Proinsulin is later divided into insulin and C-peptid D Insulin is mainly released from the cells by diffusion as proinsulin. Cells in the Islets of Langerhans in pancreas is responsible for secretion of insulin How is insulin released from the cells? A Insulin is mainly released from the cells by exocytosis after proinsulin is divided into insulin and C-peptid B Insulin is mainly released from the cells by diffusion after proinsulin is divided into insulin and C-peptid C Insulin is mainly released from the cells by exocytosis as proinsulin.E Ca2+ influx from extracellular compartment Corrects answer: E 26. Two major forms of diabetes are named type 1 and type 2.complex B Gene coding for insulin C Genes regulating glucose uptake D Genes regulating glucose metabolism Corrects answer: A 27. Which of the following hormones increases the blood glucose levels? A thyroxin B testosterone C glucagon 13 . while other hormones increase the blood glucose level. The main genetic risk in type 1 diabetes is tied to A Genes in the HLA . Insulin lowers the levels of blood glucose.

Why do one ore more tumor suppressor genes have to be inactivated in the development of a tumor? A Because tumor suppressor genes bind oncogenes in a cell B Because tumor suppressor genes are inherited in only one copy C Because tumor suppressor genes induce cell cycle halt and/or apoptosis D Because tumor suppressor genes lead to less expression of IgH (immunoglobulin Heavy Chain) in cells E Because tumor suppressor genes inhibit cell adhesion to basal membranes Corrects answer: C 32.D estradiol Corrects answer: C 30. Which property of these genes is responsible for effect? A Oncogenes regulate cell growth B Oncogenes regulate cell death C Oncogenes encode tyrosine kinases D Oncogenes encode tyrosine phosphatases E Oncogenes regulate antibody production Corrects answer: A 31. A set of related protein sequences can be represented for example by a consensus sequence (representative single sequence) or by a profile. What is the main advantage from using a profile compared to a consensus sequence? A Searching with profiles will only return related (homologous) sequences B It is not possible to search with a consensus sequence 14 . Inheritance of one deficient allele for a tumor suppressor gene may predispose for cancer Why is this? A The tumor suppressor genes are present in only one copy B Having one deficient allel destroys the expression of other genes C Having only one healthy allel increases the risk for loss of gene function D The mutated allele suppresses the healthy allele Corrects answer: C 33. The term oncogenes is used on genes that when mutated promote oncogenesis. We use the term tumor suppressor genes on genes that prevent tumor development.

and via the endosomal sorting complex required for transport (ESCRT). and what component is vital for the binding of this protein to the limiting membrane of the EE? A Hepatocyte growth factor-regulated substrate (HRS). profiles and consensus sequences perform equally well Corrects answer: C 34. and clathrin B Clathrin. where signalling can no longer occur. Why may a low-complexity protein sequence give problems in Blast? A It will give too few hits in the score matrix B Only high-complexity sequences may cause problems C The sequence is often short. and will therefore return few significant hits D It will give a complex sequence alignment that is difficult to interpret E The sequence may have a very atypical distribution of amino acids Corrects answer: E 36. transferred onto intra luminal vesicles of the EE. What is the name of the key protein for the recognition of ubiquitinated receptors on the limiting membrane of the EE. and phosphatidylinositol 3-phosphate (PI(3)P) 15 . What does an E-value of 10 in a PSI-Blast search mean? A The score value is among the 10% best values measured over the full sequence library B We can expect the on average 10 sequences from the data base get equally good or better score value if we search with a randomized sequence C Only the 10 first hits in the PSI-Blast result are significant D We can expect a minimum of 10 significant hits per data base E We have to use 10 PSI-Blast iterations to get a statistically significant result Corrects answer: B 35. Endocytosis of signalling receptors is a way of limiting signalling.C Profiles make it possible to distinguish between conserved and non-conserved positions in the sequences D Profiles are easier to implement in iterative methods E There are no specific advantages. in particular regarding level of complexity. Following endocytosis ubiquitinated receptors are recognized at the early endosome (EE). When Blast or PSI-Blast are used for comparing sequences we have to take sequence properties into account. When using for example Blast or PSI-Blast to search with an individual sequence in a library of sequences we often evaluate the result based on an E-value.

The Toll-like receptors (TLRs) utilize leucin-rich repeat motifs in the extracellular domain for ligand binding. 38. All receptors are proteins that upon binding trigger a biological response. Three enzymes participate in ubiquitin attachment to a protein substrate. and a shared intracellular domain called the Toll/interleukin-1 receptor domain (TIR)-domain for the recruitment of TIR-adapters for the initiation of intracellular signaling pathways. What toll-like receptor (TLR) is vital for the initiation of LPS signalling? A TLR3 B TLR5 C TLR4 D TLR9 Corrects answer: C. and PI(3)P D Early endosomal antigen-1 (EEA1). The E1 ubiquitin-activating enzyme. What is the name of the TIR-adapter used for signaling by most of the TLRs? A TRAM (TRIF-related adaptor molecule) B TRIF (TIR-domain-containing adapter-inducing interferon-β) C MYD88 (Myeloid differentiation primary response gene (88)) D TIRAP (TIR. E2 ubiquitin-conjugating enzyme and E3 ubiquitinprotein ligase (E3-ligase). and PI3P Corrects answer: C 37.domain-containing adaptor protein) Corrects answer:C.C HRS. What is the name of a compound that binds a receptor and triggers its biological response? A Competitive agonist B Agonist C Competitive antagonist D Antagonist Corrects answer: B 40. It is the E3-ligase that shows the substrate specificity. A major component of the gram-negative bacterial wall is lipopolysaccharide (LPS). How many E3–ligase genes are there in the human genome? A More than 500 16 . 39.

B 40 C 1 D 2 Corrects answer: A 17 .