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1B. Transmission of Genetic Information From the Gene to the Protein

DNA to RNA to protein drawn as machinery: forks that open, introns that loop out, ribosomes that ratchet, and the operons that switch it all on.

26 topics · 106 questions

Each topic is a path, not a menu: work down it in order and every question builds on the one above. Click any of them to watch the answer draw itself.

1B. Nucleotides, the Sugar-Phosphate Backbone and the Double Helix

  1. How it worksHow do purines and pyrimidines pair so that every rung of the ladder comes out the same width?
  2. How it worksWalk me through how a phosphodiester bond ties the 3 prime carbon of one sugar to the 5 prime of the next.
  3. Worked exampleFind the percentage of each of the four bases in a DNA sample that is 22 percent adenine.
  4. Common mistakeWhy isn't a nucleoside the same thing as a nucleotide?
Your turneasy1 of 3
A double-stranded DNA sample is 29 percent adenine. Using Chargaff's rules, what percentage of its bases are guanine?

1B. DNA Denaturation, Reannealing and Hybridization

  1. How it worksHow does a melting curve creep upward and then jump as hydrogen bonds give way together?
  2. Worked exampleFind which sample melts first: one that is 60 percent GC or one that is 35 percent GC.
  3. Going furtherWhat happens when you cool a melted mixture of human and mouse DNA back down slowly?
Your turnmedium1 of 3
For a DNA oligonucleotide, melting temperature can be estimated as Tm = 69.3 + 0.41 times the GC percentage minus 650 divided by the length. What is the Tm, in degrees C, of an oligonucleotide 46 bases long that is 58 percent GC?

1B. DNA Replication: Origins, the Fork and Semiconservative Copying

  1. How it worksHow do helicase, topoisomerase and single-strand binding proteins each keep the fork open?
  2. How it worksWalk me through why DNA polymerase cannot begin a strand until primase lays down a bit of RNA.
  3. Worked exampleFind how long one bidirectional origin needs to copy 4.6 million base pairs at 1000 bases per second.
  4. Going furtherWhat happens at the fork when topoisomerase is knocked out and the helix ahead keeps twisting?
  5. Common mistakeWhy isn't replication conservative, leaving the original helix whole and building a brand new one?
Your turnmedium1 of 3
A circular bacterial chromosome of 7 million base pairs is copied from a single origin, with two forks moving in opposite directions at 1000 bases per second each. How many seconds does one full round of replication take?

1B. Leading and Lagging Strands and Okazaki Fragments

  1. How it worksHow does the lagging strand loop back so one moving complex can copy both strands at once?
  2. How it worksWalk me through how RNA primers get removed and Okazaki fragments get sealed into one strand.
  3. Common mistakeWhy doesn't DNA polymerase simply work 3 prime to 5 prime on the lagging strand instead?
  4. Going furtherWhat happens to the lagging strand in a cell whose DNA ligase has stopped working?
  5. Worked exampleFind how many Okazaki fragments a 2000 base pair stretch needs at 200 bases per fragment.
Your turneasy1 of 3
A 4543 base pair stretch of lagging strand is built as Okazaki fragments averaging 230 bases each. How many fragments are made?

1B. Replicating the Ends of DNA: Telomeres and Telomerase

  1. How it worksHow does telomerase carry its own RNA template and extend the very end it is copying?
  2. Common mistakeWhy isn't the end-replication problem solved by laying one more primer at the very tip?
  3. Going furtherWhat happens to a cell's lifespan when telomerase is switched back on in adult tissue?
Your turneasy1 of 3
A somatic cell starts with 9571 base pairs of telomere and loses 147 base pairs at each division. How many divisions can it complete before the telomere is exhausted?

1B. Proofreading and Mismatch Repair

  1. How it worksHow does the polymerase back up and chew out a wrong base with its 3 prime exonuclease?
  2. Common mistakeWhy isn't a mismatch repaired by simply picking whichever base looks more likely to be correct?
  3. Worked exampleFind the final error rate when a polymerase errs once per 100000 bases and proofreading catches 99 percent.
  4. Going furtherWhat happens to a cell line when both of its mismatch repair genes are knocked out?
Your turnhard1 of 3
A DNA polymerase inserts a wrong base once every 106 nucleotides, and its proofreading exonuclease removes 96 percent of those errors before synthesis continues. After proofreading, how many nucleotides are copied per surviving error?

1B. Excision Repair and Double-Strand Break Repair

  1. How it worksHow does nucleotide excision repair cut out a whole patch of strand and rebuild it?
  2. Worked exampleFind which repair pathway handles a uracil sitting where a cytosine used to be.
  3. Going furtherWhat changes when both strands snap at once and no intact template is left behind?
  4. Common mistakeWhy isn't nonhomologous end joining as safe as homologous recombination for mending a break?
Your turneasy1 of 3
A skin cell carries 3029 thymine dimers after a day in the sun. A xeroderma pigmentosum cell repairs only 28 percent of them. How many dimers remain unrepaired in that cell?

1B. The Genetic Code: Codons, Degeneracy and Wobble

  1. How it worksHow does the third base of a codon end up mattering far less than the first two?
  2. Worked exampleFind the peptide encoded by an mRNA reading AUG GCU UUA UGC UAA.
  3. Common mistakeWhy isn't a degenerate code the same thing as an ambiguous one?
  4. Going furtherWhat happens to the wobble rule when a single tRNA has to read four different codons?
Your turneasy1 of 3
Suppose a genetic code used 4 bases per codon, drawn from the same four-letter alphabet. How many distinct codons would that code contain?

1B. Reading Frame and the Types of Mutation

  1. How it worksHow does the ribosome's fixed starting point make every downstream codon depend on the frame?
  2. Worked exampleFind what changes in the protein when GAG becomes GTG at the sixth codon of beta-globin.
  3. Worked exampleFind whether a change from UGG to UGA counts as silent, missense, nonsense or frameshift.
  4. Common mistakeWhy doesn't a silent mutation always leave the cell completely unaffected?
  5. Going furtherWhat happens when a frameshift lands so near the end that only the last few codons shift?
Your turneasy1 of 3
An open reading frame is 303 codons long, counting the terminal stop codon. How many amino acids does the finished polypeptide contain, given that the stop codon specifies none?

1B. Transcription: RNA Polymerase, Promoters and the Bubble

  1. How it worksHow does RNA polymerase find a promoter and pry open a bubble of about 17 base pairs?
  2. How it worksWalk me through how the template is read 3 prime to 5 prime while the transcript grows the other way.
  3. Worked exampleFind the mRNA transcribed from a template strand reading TACGGATCA in the 3 prime direction.
  4. Common mistakeWhy isn't the coding strand the one RNA polymerase actually reads?
  5. Ties togetherHow do the three eukaryotic RNA polymerases split the job of making mRNA, tRNA and rRNA?
Your turneasy1 of 3
RNA polymerase II transcribes a gene of 28767 nucleotides at 46 nucleotides per second. How many seconds does one transcript take to complete, ignoring initiation and termination?

1B. hnRNA Processing: the 5 Prime Cap and the Poly-A Tail

  1. How it worksHow does a backwards guanine get stuck onto the 5 prime end through an unusual linkage?
  2. How it worksWalk me through how a poly-A tail is added with no template telling it how long to be.
  3. Going furtherWhat happens to a transcript's lifespan in the cytoplasm as its poly-A tail gets chewed down?
Your turnmedium1 of 3
A primary transcript is 15143 nucleotides long. Splicing removes 2798 nucleotides of intron, and a poly-A tail of 241 nucleotides is then added. How many nucleotides long is the mature mRNA, counting the tail but not the cap?

1B. Splicing, Spliceosomes and Alternative Splicing

  1. How it worksHow does the spliceosome loop an intron out into a lariat and stitch two exons together?
  2. Worked exampleFind how many distinct proteins a four-exon gene can make when two of its exons are optional.
  3. Common mistakeWhy isn't an intron simply junk the cell never got around to deleting?
  4. Going furtherWhat happens to the protein when a point mutation destroys the splice site at an intron's edge?
  5. Ties togetherHow does alternative splicing let 20000 genes turn into many times that many proteins?
Your turnmedium1 of 3
A gene has several constitutive exons plus 6 cassette exons, each of which is independently either included or skipped. How many distinct mature mRNAs can the gene produce?

1B. tRNA Charging and Ribosome Structure

  1. How it worksHow does an aminoacyl-tRNA synthetase read both the amino acid and the tRNA before joining them?
  2. Worked exampleFind the anticodon on the tRNA that delivers methionine to the start codon AUG.
  3. Going furtherWhat happens to the growing protein when a charged tRNA has its amino acid chemically swapped?
Your turnmedium1 of 3
Charging one tRNA costs one ATP hydrolysed to AMP and pyrophosphate, which is worth two high-energy phosphate bonds. How many high-energy phosphate bonds are spent charging 44 tRNA molecules?

1B. Translation: Initiation, Elongation and Termination

  1. How it worksHow does the ribosome ratchet one codon at a time through its A, P and E sites?
  2. Common mistakeWhy doesn't a stop codon get read by a tRNA the way every other codon does?
  3. Going furtherWhat happens when several ribosomes translate the same mRNA at once as a polysome?
  4. Worked exampleFind how many high-energy phosphate bonds it costs to add one amino acid to a growing chain.
  5. Ties togetherHow does the difference between prokaryotic and eukaryotic initiation give antibiotics a target?
Your turnmedium1 of 3
Adding one amino acid to a growing chain costs two high-energy phosphate bonds to charge the tRNA and two more in GTP hydrolysis during delivery and translocation. How many high-energy phosphate bonds does a polypeptide of 145 residues cost to elongate?

1B. Post-Translational Modification and Protein Targeting

  1. How it worksHow does a signal sequence send a ribosome to dock on the rough endoplasmic reticulum?
  2. Common mistakeWhy isn't glycosylation merely decoration added to a protein's outer surface?
  3. Going furtherWhat changes about a protein's fate once a chain of ubiquitins gets attached to it?
Your turneasy1 of 3
A secreted protein is translated as a precursor of 472 residues, and signal peptidase then removes an amino-terminal signal sequence of 25 residues. How many residues does the mature protein contain?

1B. Nucleosomes, Supercoiling and Chromosome Organization

  1. How it worksHow does DNA wrap nearly twice around a histone octamer to make one nucleosome bead?
  2. Going furtherWhat happens to a gene buried in packed heterochromatin when transcription factors come looking?
  3. Worked exampleFind how many nucleosomes a 30000 base pair region holds at about 200 base pairs each.
  4. Common mistakeWhy isn't supercoiling merely a tangle the cell would be better off without?
Your turneasy1 of 3
A region of chromatin spans 44821 base pairs, and one nucleosome plus its linker accounts for about 200 base pairs. How many nucleosomes does the region contain?

1B. The lac Operon and Positive Control

  1. How it worksHow does lactose knock the repressor off the operator and let transcription run?
  2. How it worksWalk me through how low glucose raises cyclic AMP and lets CAP crank the promoter up.
  3. Common mistakeWhy doesn't lactose alone give full expression when glucose is also on the table?
  4. Worked exampleFind what happens to lac expression in a mutant whose operator can no longer be bound.
  5. Ties togetherHow do negative and positive control combine so one promoter answers two different sugars?
Your turneasy1 of 3
An operon carries 5 structural genes transcribed together as a single polycistronic mRNA, each gene with its own start and stop codons. How many separate polypeptides are made from one such transcript?

1B. The trp Operon: Repressible and Inducible Control

  1. How it worksHow does tryptophan act as a corepressor that only lets the repressor bind once it is around?
  2. Going furtherWhat happens to trp transcription the moment the amino acid supply runs out?
  3. Common mistakeWhy isn't a repressible operon the same as a negatively controlled inducible one?
  4. Ties togetherHow do lac and trp end up as mirror images of the very same repressor logic?
Your turneasy1 of 3
A culture growing in medium with 145 micromolar tryptophan is washed into medium with none. What happens to trp operon transcription?

1B. Eukaryotic Transcription Factors, Enhancers and Silencers

  1. How it worksHow does DNA loop around so a distant enhancer physically touches the promoter it controls?
  2. How it worksWalk me through how a transcription factor's binding domain recognizes one specific sequence.
  3. Going furtherWhat changes about expression when the same enhancer is active in one tissue and silent in another?
Your turnmedium1 of 3
An enhancer lies 59 kilobase pairs from the promoter it controls. At 0.34 nanometres of contour length per base pair, how many micrometres of DNA lie between them along the double helix?

1B. Chromatin Remodelling, DNA Methylation and Histone Acetylation

  1. How it worksHow does acetylating histone tails loosen their grip on DNA and open a gene up?
  2. Common mistakeWhy doesn't DNA methylation change the sequence of the gene it silences?
  3. Common mistakeWhy isn't an epigenetic mark wiped clean every time the cell divides?
  4. Going furtherWhat happens to gene expression when a drug blocks every histone deacetylase in a cell?
Your turneasy1 of 3
A CpG island contains 151 CpG dinucleotides, and 62 percent of them are methylated on the cytosine of the top strand. How many methyl groups does that amount to on the top strand?

1B. Non-Coding RNA and Post-Transcriptional Control

  1. How it worksHow does a microRNA pair with a transcript and mark it for silencing or destruction?
  2. Common mistakeWhy isn't every RNA molecule in a cell on its way to becoming a protein?
  3. Going furtherWhat happens to a target gene when a small interfering RNA matching it is introduced?
Your turneasy1 of 3
A transcriptome study finds that 87 percent of the RNA a cell makes never encodes a protein. What are those transcripts doing?

1B. Cancer as a Failure of Normal Cellular Controls

  1. How it worksHow does a proto-oncogene turn into an oncogene through mutation, amplification or translocation?
  2. Common mistakeWhy isn't a tumor suppressor gene something that causes cancer when it is working properly?
  3. Going furtherWhat happens to a cell's checkpoints when p53 can no longer halt the cycle for repair?
  4. Ties togetherHow does gene amplification tie a cancer cell's genome straight to the level of expression?
Your turneasy1 of 3
A breast tumour carries 30 copies of the HER2 gene where a normal cell has 2, and expression is proportional to copy number. By what factor is HER2 expression raised relative to normal?

1B. Restriction Enzymes, Cloning Vectors and DNA Libraries

  1. How it worksHow do sticky ends from one restriction cut let two unrelated DNA pieces be pasted together?
  2. How it worksWalk me through getting a human gene into a plasmid and then into a bacterium that copies it.
  3. Worked exampleFind how many fragments a circular plasmid yields when one enzyme cuts it at three sites.
  4. Going furtherWhat changes about a library built from mRNA as cDNA rather than from genomic DNA?
  5. Common mistakeWhy isn't a cDNA library able to tell you anything at all about a gene's introns?
Your turnmedium1 of 3
A circular plasmid is digested with one restriction enzyme that cuts it at 6 sites. How many linear fragments result?

1B. The Polymerase Chain Reaction and DNA Sequencing

  1. How it worksHow do the three temperatures of one PCR cycle denature, anneal and extend the target?
  2. How it worksWalk me through how chain-terminating dideoxy nucleotides turn one template into a readable ladder.
  3. Worked exampleFind how many copies of a target 30 cycles of PCR produce starting from one molecule.
  4. Common mistakeWhy doesn't PCR need a whole cell's replication machinery to copy a piece of DNA?
  5. Going furtherWhat changes when PCR is run on RNA by making a cDNA copy of it first?
Your turnmedium1 of 3
A PCR reaction starts with 15 copies of a target and runs 23 cycles at perfect efficiency. How many copies of the target are present at the end?

1B. Gel Electrophoresis and the Blotting Techniques

  1. How it worksHow does a Southern blot move separated DNA onto a membrane and light up one band with a probe?
  2. Going furtherWhat changes when the same technique is run on RNA as a northern blot or on protein as a western?
  3. Worked exampleFind the fragment sizes when a circular 10 kilobase plasmid is cut at 2, 5 and 9 kilobases.
  4. Common mistakeWhy isn't a western blot detecting DNA, the way its family of names might suggest?
Your turneasy1 of 3
A circular plasmid 14 kilobases in size is cut at two sites, at positions 3 and 8 kilobases. How many kilobases long is the fragment that runs directly from the cut at 3 to the cut at 8?

1B. CRISPR, Gene Therapy, Transgenics and Ethics

  1. How it worksHow does a guide RNA walk Cas9 to one twenty-letter address in three billion base pairs?
  2. Going furtherWhat happens when the cut is repaired by end joining instead of from a supplied template?
  3. Worked exampleFind the off-target risk when a guide RNA matches 18 of its 20 bases somewhere else in a genome.
  4. Ties togetherHow does gene therapy's delivery problem connect to the way viruses get DNA into cells?
Your turnhard1 of 3
A guide RNA specifies a target 19 base pairs long. In a genome of 4 billion base pairs with all four bases equally frequent, how many exact matches to that target are expected by chance?

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