Sollars - DNA Structure

Question 1

What is the central dogma?

Answer 1

DNA - Transcription - RNA - Translation - Protein

Question 2

What is the general structure of DNA?

Answer 2

Polynucleotide sequence joined through 3’-5’ phosphodiester bonds. Polar primary structure, strands run antiparallel, exterior is hydrophilic, interior hydrophobic, helix has major and minor grooves

Question 3

What is often found at the 5’ and 3’ ends of DNA?

Answer 3

5’ - Phosphate 3’ - Hydroxyl

Question 4

What is the role of Actomycin D?

Answer 4

Anticancer drug which intercalates b/t the planar bases of DNA

Question 5

What are Chargaff’s Rules?

Answer 5

A=T, G=C, Purines = Pyrimidines (A+G=T+C)

Question 6

What is a major exception to Chargaff’s Rules?

Answer 6

Base composition in an organism can be affected by environment, age, and/or nutrition

Question 7

What are the hydrogen bonding rules in DNA? What does this result in?

Answer 7

A-T = 2 G-C = 3 Sequences rich in A-T pairings will be weaker than those rich in G-C pairings

Question 8

What is the most common form of DNA? What is Z-DNA? A-DNA?

Answer 8

B-DNA

Z-DNA: Left handed double helix rich in G-C

A-DNA: Made by dehydrating B-DNA, found in RNA hybrids or RNA-RNA double strands

Question 9

What has an impact on viscosity and UV-absorption? What is this called, and how is it used?

Answer 9

Denaturation Hyperchromic Effect, used as standard to measure purity of DNA in preparations

Question 10

Is melting point uniform for strands of DNA?

Answer 10

No, elevation/depression depends on differences in A/T , G/C rich regions (2 vs 3 hydrogen bonds)

Question 11

What is Chromatin?

Answer 11

Complex of nucleic acids (DNA/RNA) and proteins (histones/nonhistones) comprising eukaryotic chromosomes

Question 12

What is the role of histones in DNA secondary structure?

What is their electrochemical makeup?

What is the role of Histone H1?

Answer 12

DNA wraps around histone complexes to form nucleosomes

Large amounts of basic amino acids (H, K, R) leading to a positive charge which attracts negatively charged DNA

Histone H1 associated with linker DNA b/t nucleosomes, induces positive supercoiling in the linker region

Question 13

What are the two types of Chromatin?

Answer 13

Euchromatin - loosely packed, transcriptionally active

Heterochromatin - tightly packed, transcriptionally inactive

Question 14

What occurs when the axis of the DNA helix is coiled on itself?

What types of this are there?

What must cells do as a result?

Answer 14

Supercoiling

Positive - Winds in same direction as helix

Negative - Winds in opposite direction as helix

Cells must actively maintain an unwound state necessary to facilitate access to DNA

Question 15

What class of molecules relax supercoiling stress?

What type of supercoiling to they maintain? How?

Answer 15

Topoisomerases

Maintain Negative Supercoiling by breaking DNA then resealing the breaks

Question 16

What does Ciprofloxacin target?

Answer 16

Bacteria topoisomerase

Question 17

What does doxorubicin target?

Answer 17

Human type II topoisomerase inhibitor

Question 18

What drives the differences in packaging in viruses, bacteria, and higher organisms?

Answer 18

Genome size.

In humans, DNA is organized in chromosomes; in mitochondira and backteria they are circular (which are also loosely termed chromosomes)

Question 19

Centromere

What is different about metaphase?

Answer 19

Region to which spindle traction fibers attach during mitosis/meiosis.

Joining point for two replicated chromatids

During metaphase, centromere is narrower than distal regions, termed primary chromosomal constriction

Question 20

Telomere

Answer 20

Repeated DN sequence w/specialized proteins found and ends of eukaryotic chromosomes; chromosomes lose 100 nucleotides from ends per cell division (can be repaired by some cells)

Question 21

Origin of Replication

Answer 21

Nucleotide sequence at which DNA syntheis begins, multiple sites in humans

Bacteria only have one due to circular chromosome

Question 22

Rett Syndrome

Answer 22

X-linked genetic disorder observed in females; 99% of cases are mutations–lack of reproductive function.

Cause: Defect in methyl-CpG-binding protein 2, involved in chromatin formation—DNA packaging error

Question 23

What is Royal Jelly an example of?

Answer 23

Epigenetics–also a deviation from Chargaff’s rules

Question 24

DNA Methylation

Where does it usually occur?

What is the usual result?

Answer 24

Acts to sterically inhibit interaction with DNA molecules and further serve as a binding site for proteins

Usually occurs in the promoter region

Usually silences genes–but may also activate

Question 25

DNA Methyltransferases (DNMTs)

Answer 25

Catalyze DNA methylation using S-adenosyl methionine (SAMe) as donor

Question 26

Ten-Eleven Translocation (TET) Enzymes

Answer 26

Remove methylation

Question 27

Thymine-DNA Glycolase (TDG)

Answer 27

Removes thymine moieties from G/T mismatches by hydrolyzing the carbon-nitrogen bond

Question 28

What modification is occuring in Histone Modification? How does it occur? What is the result? What major enzymes cause this to occur?

Answer 28

Acetylation Transfer of acetyl group from **Acetyl Co-A** to **E-amino group of lysine** Partial neutralization of the (+) charge on histon, decreasing affinity to DNA HAT (+ acetyl) HDAC (- acetyl)

Question 29

HATs / HDACs

Answer 29

Histone Acetylransferases (HATs) - add acetyl to histone Histone Deacetylase (HDACs) - remove acetyl from histone

Question 30

How are hypomethylating agents used? What does it do?

Answer 30

Treatment of some medically fit patients with adverse features of AML **Blocks DNA Methyltransferae** (Inhibits DNA methylation)

Question 31

HDAC Inhibitors?

Answer 31

Used in some individuals with lymphoid malignancies, such as multiple myeloma and Sezary Syndrome