Chapter 7: Nucleic Acids
All cells require RNA production , even if they are not growing in order to continually replenish degraded RNA. RNA does not contain thymine, but DNA does. Thus if thymine production is blocked, only DNA replication will be inhibited and only rapidly dividing cells such as cancer cells will be affected
Anticancer drugs often seek to block growth of rapidly dividing cells by inhibiting production of thymine. Why is this an attractive target for cancer therapy?
No, in dilute solution they will be H-bonded to water
Both purines and pyrimidines have abundant hydrogen bonding potential. Will adenine and thymine H-bond with each other in dilute aqueous solution (0.1 M for example)?
chromatin
Fully packed DNA is called what?
they are covalently linked by phosphodiester bonds between the 3' hydroxy group of the sugar in one nucleotide and the 5' phosphate group of the sugar in the next nucleotide
How are the nucleotides in nucleic acids linked together?
once every 34 angstroms, or every 10 base pairs
How often does the helix pattern of DNA repeat itself (complete a full turn)?
since one angstrom is 10^-10 meters, the length is (3.4 x 10^-10 meters/base pair) x (9 x 10^7 base pairs) = 30 x 10^-3 meters or 30 millimeters
If a human chromosome has 9x10^7 base pairs, how long would the chromosome be if it were stretched out completely?
3 billion x 1 SNP/1000 bases = 3 million human SNPs
If the size of the human genome is just over 3 biillion base pairs approximately how many human SNPs are there?
The charged phosphates electrostatically repel each other in normal DNA. Methyl esters will not be charged. The lack of electrostatic repulsion between the methyl ester backbones will increase Tm, meaning that more kinetic energy will be required to melt the oligonucleotides
If you attached methyl groups to all the acidic phosphate oxygens along the length of a DNA double helix, would the chain have a higher or lower Tm than normal DNA?
a beta linkage indicates that the anomeric carbon has a configuration with the attached group (a nitrogen of the aromatic ring of a purine or pyrimidine base) drawn ABOVE the plane of the ribose ring (it's better to B up)
In the beta-N-glycosidic linkage of a nucleoside, is the aromatic base above it or is it below the plane of ribose in a Hawthorne projection?
single nucleotide polymorphisms (SNPs)
It's predicted that there are changes in a single nucleotide once in every 1,000 base pairs in the human genome. What are these variations called?
acrocentric
Linked chromatids that are composed of extended q (long) arms with minimal p (short) arms would be best described as:
3
Phosphoric acid has the potential to donate how many protons?
The single stranded DNA is found at the very end of the chromosome and loops around to form a knot to stabilize the end of the chromosome
Telomeres are composed of both single and double stranded DNA. Where is the single stranded DNA found, and what does it do?
pyrimidines hydrogen bond to purines and a strand in its 5' to 3' orientation is paired with a strand in a 3' to 5' orientation
The DNA double helix is described as being both complementary and antiparallel. What characteristics of the polynucleotide generate these properties respectively?
True - for every G there is a C, and for every A there is a T
True or false? If the amount of G in a double helix is known, the amount of C can be calculated
False - the ratio of purines to pyrimidines is always the same (50:50) since each purine is paired with a pyrimidine. In order to calculate the amount of any one base, you have to know the ratio of AT to GC pairs
True or false? If the fraction of purine nucleotides and the total molecular weight of a double helix are known, the amount of cytosine cane be calculated
False - the ratio or purines to pyrimidines is always the same - 50:50
True or false? The two chians in a piece of ds-DNA containing mostly purines will be bonded together more tightly than the two chains in a piece of ds-DNA containing mostly pyrimidines
CNVs are structural variations in the genome that lead to different copies of DNA sections. Large regions of the genome can be duplicated or deleted by these variations
What are Copy-number variations (CNVs)?
regions composed of noncoding DNA that separate the regions of the genome with high transcription rates. They may direct the assembly of specific chromatin structures and can contribute to the regulation of nearby genes, but many have no known functions
What are intergenic regions?
regions where short sequences of nucleotides are repeated one right after the other, from as little as 3 to over 100 times
What are tandem repeats?
the region at the ends of linear chromosomes distinguished by the presence of distinct nucleotide sequences repeated 50 to several hundred times. The repeated unit is usually 6-8 base pairs long and guanine rich.
What are telomeres?
annealing or hybridization
What are the 2 terms used for the binding of 2 complementary strands of DNA into a double-stranded structure?
melting or denaturation
What are the 2 terms used for the separation of DNA strands?
1. when phosphates are linked together, their negative charges repel each other strongly 2. orthophosphate has more resonance forms and thus a lower free energy than linked phosphates 3. orthophosphate has a more favorable interaction with the biological solvent (water) than linked phosphates
What are the 3 reasons why phosphate anhydride bonds store so much energy?
guanine and adenine, a double-ring structure (a 6-membered ring and a 5-membered ring)
What are the purines and what does their structure consist of?
cytosine, thymine, and uracil; a single 6-membered ring (CUT the Py)
What are the pyrimidines and what does their structure consist of?
Transfer RNA (tRNA), which is responsible for translating the genetic code by carrying amino acids from the cytoplasm to the ribosome to be added to a growing protein, and Ribosomal RNA (rRNA), which serve as components of the ribosome, some of which provide catalytic function (ribozymes)
What are the two major types of noncoding RNA and what do they do?
a ribose (or deoxyribose) sugar group; a purine or pyrimidine base joined to carbon number 1 of the ribose ring; and one, two, or three phosphate units joined to carbon 5 of the ribose ring
What does the structure of a nucleotide consist of?
the temperature at which a solution of DNA molecules is 50 percent melted
What is Tm?
they function as disposable buffers, blocking the end of chromosomes to prevent chromosome deterioration and prevent fusion with neighboring chromosomes.
What is the function of telomeres?
DNA is wrapped around globular proteins called histones to form nucleosomes
What is the mechanism eukaryotes use to package DNA densely in order to fit within the cell?
An enzyme called DNA gyrase uses the energy of ATP to twist the gigantic circular molecule into twists called supercoils
What is the mechanisms prokaryotes use for making their circular chromosome more compact and sturdy?
messenger RNA - carries genetic information to the ribosome where it can be translated into protein
What is the only type of coding RNA and what does it do?
tandem repeats can become unstable when the repeating unit is short or when the repeat itself is very long. This can lead to chromosome breaks
When do tandem repeats become unstable, and what can result from this instability?
non-coding regions
Where do SNPs occur most frequently?
the end of the chain with a free 5' phosphate group is written first with the other nucleotides in the chain indicated in the 5' to 3' direction
Which end of a polynucleotide is written first?
During polymerization of nucleoside triphosphates, pyrophosphate is released and hydrolyzed, driving the polymerization reaction forward. Hydrolysis of the high-energy pyrophosphate makes the polymerization of. nucleoside triphosphates more energetically favorable
Which reaction is more thermodynamically favorable: the polymerization of nucleoside monophosphates, or the polymerization of nucleoside triphosphates?
The RNA polymer is less stable, because the 2' hydroxyl can nucleophilically attack the backbone phosphate group of an RNA chain, causing hydrolysis when the remainder of the chain acts as a leaving group. This cannot occur in DNA because there is no 2' hydroxyl
Why are RNA polymers less stable than than DNA polymers?
DNA coiling places inside the tube-like structure of the double helix, where they interact with each other
Why do the nucleic bases not interact with water when they are in DNA?
the Tm of the first oligonucleotide would be lower because it contains more AT pairs. A and T only form 2 hydrogen bonds while G and C form 3. Thus it takes less kinetic energy to disrupt A-T rich ds-DNA than G-C rich ds-DNA
Would the Tm of ATTATCAT and its complementary strand be higher than, lower than, or equal to the melting temperature of ACTCGCAT?
The 2' OH is missing in deoxyribose
how does the structure of deoxyribose compare with that of ribose?
It has a sequence containing introns and exons and requires addition of a cap and tail and splicing
what is a defining characteristic of heterogenous nuclear RNA (hnRNA), the precursor to messenger RNA?