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110 Cards in this Set
- Front
- Back
The interconversion between mono and diphoshpate nucleotides if mediated by _____________________________>
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specific nucleoside monophosphate kinases (one for every base)
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The interconversion between di- and triphosphates is mediated by ___________________, called ____________________.
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a single kinase, nucleoside diphosphate kinase (NDPK)
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CTP is created from UTP with which enzyme? how is this enzyme regulated?
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cytidine triphosphate synthetase (cytidylate synthetase), CTP is the feedback inhibitor
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In pyrimidine biosynthesis carbamoyl phosphate and aspartate synthesize ______________ _______________. What is the name of the enzyme? How is it regulated?
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carbamoylaspartate, enzyme= aspartate transcarbamoylase , regulated by CTP
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Where does the amine group on the 4C of CTP come from?
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Gln, Q
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ATCase? what is it? how is it regulated?
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carbamoyl apartate, makes carbamoyl aspartate from
carbamoyl phosphate, it is down regulated by CTP, upregulated by ATP in the presence of CTP |
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CO2
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Glycine
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n10-fomyltetrahyrofolate
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glutamine
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aspartate
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glutamine
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n10- formyltetrahydrofolate
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glutamine
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CO2
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Aspartate
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Draw this.
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Draw this.
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PRPP amidotransferase
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Gln+H2O ----> Glu + NH3
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5-phoshoribosyl-1-amine
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committed step
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Turning PRPP into 5-phosphoribosyl-1-amine is done by which enzyme? how is it regulated?
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PRPP amidotransferase
regulation partial- GTP ATP total - GTP & ATP IMP |
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enzyme? regulation?
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ribose phosphate pyrophosphokinase , downregulated by ADP
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Who performed the S & R experiment? what was the main conclusion of the experiment?
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Griffith, genetic material can be transferred between cells
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Who performed the "ase" tests? What was the main conclusion of the experiment?
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Avery, McLeod, McCarty, DNA is the "transforming principle"
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Who performed the virus experiment? What was the main conclusion from the experiment?
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Hershey, Chase, Solidified that DNA is the genetic material
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adenylosuccinate synthetase
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inosinate (IMP)
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Inosinate (IMP) dehydrogenase
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Allosteric feedback regulation of purine ribonucleotide synthesis occurs at four places. Name the enzymes.
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PRPP synthetase, glutamine-PRPP amidotransferase, adenylosuccinate lyase, IMP dehydrogenase
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Name the endproducts, missing enzymes, and draw the regulation of this pathway.
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In the purine ribonucleotide biosynthesis pathway ribose 5-phosphate is converted to PRPP. Name the enzyme, and the regulation.
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PRPP synthetase, downregulated by ADP
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In the purine ribonucleotide biosynthesis pathway PRPP is converted to 5-Phosphoribosylamine. Name the enzyme, and the regulation.
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glutamine-PRPP amidotransferase,
regulation partial- GTP ATP total - GTP & ATP IMP |
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In the purine ribonucleotide biosynthesis pathway IMP is converted to AMP. Name the regulated enzyme, and the regulation.
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adenylosuccinate synthetase, down regulated by AMP
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In the purine ribonucleotide biosynthesis pathway IMP is converted to GMP. Name the regulated enzyme, and the regulation
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IMP dehydrogenase, downregulated by GMP
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Name the enzyme reponsible for converting ribonucleotides into deoxyribonucleotides.
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ribonucleotide reductase
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Ribonucleotide reductase use _________________________ as substrates.
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ribonucleoside diphosphates
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Ribonucleotide reductase catalyzation involves a _______________ reduction. The source of these electrons is ___________________.
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2 electron, NADPH
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The regulation of ribonucletoide reductase maintains a balance of ______________________ ______________________.
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deoxynucleotide concentrations
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Regulation of _________________ ________________ maintains a balance of deoxynucleotide concentrations.
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ribonucleotide reductase
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Name this enzyme. What does it do?
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Ribonucleotide reductase
converts RNA to DNA |
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Substrate specificity site - top
Primary regulation site - bottom |
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active site
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ATP, dATP, dGTP, dTTP
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ATP, dATP
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ADP, CDP, UDP, GDP
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The primary regulation switch on ribonucleotide reductase is an ON/OFF switch regulated with ATP, dATP. Which substrate in on, off?
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on-ATP
off-dATP |
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The primary regulation switch on ribonucleotide reductase is an _________ - _________ switch.
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on/off
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The primary regulation switch on _______________ _______________ is an ON/OFF switch regulated with ATP, dATP. Which substrate in on, off?
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ribonucleotide reductase
on-ATP off-dATP. |
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The primary regulation switch on ribonucleotide reductase is an ON/OFF switch regulated with what substrates?
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on-ATP
off-dATP |
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The substrate specificity site on ribonucleotide reductase works by ________________ regulation.
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reciprocal
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The substrate specificity site on ribonucleotide reductase works by reciprocal regulation. Explain.
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If a purine is in the substrate specificity site than a primidine is in the active site and vica versa.
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The reaction in the active site of ribonucleotide reductase occurs via a ____________ _____________. Which is pointed out because there are not many of these in the human body.
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radical intermediate
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draw the regulation for Ribonucleotide reductase.
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dTMP is derived from d_______.
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UMP
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Fill in the blanks of this pathway for dTMP.
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_____________ ______________ catalyzes the last step in dTMP pathway, the reaction uses THF as the cofactor to add a ____________ ____________ to C5. It converts d_____ to dTMP.
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Thimidylate Synthase
methyl group |
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This pathway is the target for several ___________ and ______________ drugs.
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cancer, autoimmune
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____________ aa residue methylates Tetrahydrofolate.
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Serine
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Many types of cancers are defined by _____________ ___________ cells.
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rapidly dividing
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Cell division requires replication of ____________ ________, thus cancer (or rapidly dividing cells have a heightened need for _______________.
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genomic DNA, nucleotides
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Failure to replicate DNA during the cell cycle is detected by the DNA replication checkpoint resulting in _____________ _____________ ___________ and/or ______________.
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cell cycle arrest, apoptosis (programmed cell death)
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Because cancer is often rapidly dividing, blocking ___________ precursors is an effective strategy to arrest the cell cycle and/or cause apoptosis.
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nucleotide precursors
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Two specific strategies of blocking nucleotide precursors to eliminate cancer are?
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1. Block (Q) PRPP amidotransferase by using Q analogs, halting purine production
2. Block thymidylate synthase, stopping dTMP production. |
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Describe how Fluorouracil halts nucleotide metabolism.
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Fluorouracil becomes FdUMP though the de novo pyrimidine pathway covalently binding to thymidylate synthetase halting the production of dTMP.
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Describe how Methotrexate inhibiits nucleotide metabolism.
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Methotrexate halts the methylation of THF that produces N5,N10 methylene THf. It does this by having a higher binding affinity for dihydrofolate reductase than it's substrate. Thus halting the production of dTMP.
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Name the two cancer treatment drugs that inhibit dTTP production.
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Fluorouracil
Methotrexate |
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Name the two cancer treatment drugs that inhibit purine biosynthesis.
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azaserine
avicin |
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Free __________ and ___________ bases can be salvaged from degraded DNA and RNA.
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purine, pyrimidine
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In the salvage pathway for purines.
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Adenosine phosphoriboysltransferase
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In the salvage pathway for purines Guanine or (hypoxyanthine) + PRPP --> GMP or XMP + PPi is catalyzed by ______________ _______________________(H/GPRT).
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hypoxanthine/guanine phosphoribosyltranferase.
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the best studied are ___________ salvage pathways which use specific __________________________ to join PRPP to free purine bases to form nucleotide monophosphates.
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purine, phosphoribosyltransferases
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In the catabolism and salvage of nucleotides pathway, guanylate and adenylate have a shared breakdown product in _______________.
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xanthine
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In the catabolism and salvage of nucleotides pathway, _______________ and ______________ have a shared breakdown product in xanthine.
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guanylate and adenylate
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In the catabolism and salvage of nucleotides pathway, guanosine cleavage from ribosyl produces the free base ____________, which is then deaminated to form ____________.
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guanine, xanthine
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In the catabolism and salvage of nucleotides pathway, adenosine is deaminated to form ___________. Separation from ribose yields _______________, which is oxidized to form _____________.
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inosine, hypoxanthine, xanthine
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The end product of the degradation of purines is?
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uric acid
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________ is the swelling of joints resulting from a build-up of urate in the form of sodium urate crystals.
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Gout
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Gout is the swelling of joints resulting from a build-up of ________ in the form of __________ __________ crystals.
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urate, sodium urate
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Gout is caused by the ________________ of uric acid.
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undersecretion or overproduction
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Gout, which is caused by undersecretion of uric acid is the result of a genetic defect. This defect is not known but is likely related to improper _______________ balance.
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purine
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What drug is used in the treatment of gout?
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Allopurinol
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The gout treatment drug Allopurinol is an anolog to _________________.
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Hypoxyanthine
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Allopurinol metabolizes to ____________, it is catalyzed by xanthine oxidase. ____________ binds tightly to ____________ ____________ effectively blocking the active site.
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oxypurinol, xanthine oxidase
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The cancer treatments and gout treatments talked about in class are called _____________________________. (general name)
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mechanism based inhibition or suicide substrate inhibition
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Define phenotype?
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the observable characteristics of an organism
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Define gene?
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a chromosomal segment that codes for a single functional polypeptide chain or RNA molecule
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Define chromosome?
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a single large DNA molecule and its associated proteins (contains many genes)
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Define karyotype?
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the number and visual appearance of the chromosomes in the cell nuclei of an organism or species
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Define genome?
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all the genetic information encoded in a cell or virus
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m-phase, chromatids, centromer, condensed
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What is the c-value enigma?
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Telomeres
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Centromere
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genes, repeats, origins of replication
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Current estimates are that ______% of the genome codes for genes. ______% is noncoding.
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30 , 70
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Of the 30% that encodes for genes, only _____% is actually coding sequence, the remaining ______% consists of ___________ which are removed after transcription.
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1.5 , 28.5 , introns
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Approximately ____% of our genome is transposons.
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45%
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Evidence for non-coding, repeated elements in the DNA comes from?
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FISH analysis, Cot curves, Genome sequencing
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In DNA supercoiling these two are called?
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twist and writhe
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For B-form dsDNA any deviation from a helical twist of 10.5bp/turn represents a ____________ ____________.
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strained conformation
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Most dsDNA in a cell is _______________ resulting in writhe.
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underwound
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In supercoiling, _________ is the number of turns of the DNA double helix.
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twist
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In supercoiling, ______________ is the munber of times a dsDNA molecule is coiled or crosses over itself.
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writhe
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Why is it that many circular DNA molecules remain supercoiled when extracted from cells and free of protein and other cellular components?
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because the dsDNA is underwound
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