Lecture 7: Nucleic Acid Structure I

Question 1

Primary DNA structure

Answer 1

single strand of bases

Question 2

Secondary DNA structure

Answer 2

-helix
-stem loop
-pseudoknot

Question 3

Tertiary DNA structure

Answer 3

-A, B, Z forms
-stem loop and psuedoknot

Question 4

Quaternary DNA structure

Answer 4

-DNA around a histone
-RNA with monomers

Question 5

purine bases

Answer 5

-adenine
-guanine

Question 6

pyrimidine bases

Answer 6

-cytosine
-thymine
-uracil

Question 7

Non B-form DNA structures

Answer 7

-form transiently during replication, recombination, or transcription
-ex: triplex DNA/H-DNA
-can cause DNA polymerase to stall = nicks, breaks, possible malfunction

Question 8

triplex DNA/H-DNA

Answer 8

-G-quadruplex structures in guanine-rich regions of DNA
-i-motif in cytosine-rich region of DNA
-expanded triplex sequences

Question 9

Expanded triplex sequences

Answer 9

can cause certain hereditary neurological diseases

Question 10

G-quadruplex and i-motif structures

Answer 10

-essential roles in regulating transcription and genome stability
-disruption can lead to cancer and aging

Question 11

Topoisomerases

Answer 11

-maintain DNA supercoiling
-target of anticancer drugs

Question 12

B-DNA structure

Answer 12

-base pairing
-base stacking
-most stable under physiological conditions
-elongated and narrower than A
-larger degree of twist

Question 13

A-DNA structure

Answer 13

-observed under dehydrating conditions and high salt
-compatible with RNA
-compressed and wider

Question 14

B-DNA major binding groove

Answer 14

-wider and shallower than A
-highly accessible for proteins to bind

Question 15

Major and minor grooves

Answer 15

SLIDE 8 adn SLIDE 9

Question 16

Double stranded DNA

Answer 16

-conformationally flexible

Question 17

Helix features A vs B

Answer 17

SLIDE 10

Question 18

A-form DNA

Answer 18

-less solvent exposure
-under dehydrating conditions
-protects it under desiccating conditions
-often occurs in formation of DNA-RNA hybrid helix

Question 19

SIRV2 virus protein

Answer 19

-certain protein that dehydrates DNA upon binding = A-form
-infects hyperthermophilic acidophile sulfolobus islandicus

Question 20

DNA deformability

Answer 20

-structure can deviate locally (around a few bps) when bound to small molecules while still maintaining base pairing
-intercalators
-groove binders

Question 21

Intercalators

Answer 21

-hydrophobic
-heterocyclic
-insert between bases through ring stacking
-Ex: TOTO

Question 22

TOTO

Answer 22

-intercalator
-fluorescent label used to detect dsDNA in gels

Question 23

Minor-groove binders

Answer 23

-outnumber major-groove binders
-ex: Netropsin
-some groove binders change twist

Question 24

Netropsin

Answer 24

-antibiotic and antiviral
-interacts with sugars and an edge of the bases giving sequence-specific binding

Question 25

DNA intercalating agents

Answer 25

-interfere with DNA replication, transcription and repair -distortions to DNA structure also lead to mutations = mutagens -Actinomycin D

Question 26

Actinomycin D

Answer 26

-chemotherapeutic agent -treats Wilms' tumor -pediatric kidney tumors

Question 27

Superhelical (supercoiling)

Answer 27

-created by underwinding (negative) or overwinding (positive) DNA to lowest energy helical state (thermo favored B-form) -circularized DNA after loss of bp -compacts DNA -tend to disrupt H bonding that may lead to repair and replication

Question 28

DNA activity in replication and transcription

Answer 28

-topologically supercoiled form has greater activity than relaxed B-form -supercoiling disrupts H bonding which may lead to repair and replication

Question 29

Negative supercoiling

Answer 29

-underwinding -form right-handed superhelix -easier to unwind - = repair, replication, recombination

Question 30

Positive Supercoiling

Answer 30

-overwinding -form left handed superhelix -hard to unwind -stabilizes DNA under extreme conditions

Question 31

Supercoiling equation

Answer 31

Lk = Tw + Wr -sum of Tw and Wr constant = one to one change

Question 32

Lk

Answer 32

-linking number -does not change once both ends are fixed (anchored to protein or circular DNA)

Question 33

Tw

Answer 33

-twist -turns in DNA chain -one every ~10 bp for relaxed DNA

Question 34

Wr

Answer 34

-writhe -superhelical coild

Question 35

SLIDE 19 MELTED DNA

Answer 35

SLIDE 19

Question 36

For double stranded DNA with 110 base pairs, what is the relative length of the helical structure in A-form and B-form

Answer 36

B-form is longer than A-form

Question 37

Linear DNA in eukaryotes

Answer 37

-supercoiled -anchoring by nuclear proteins created topological domains

Question 38

Linear DNA supercoiling

Answer 38

-induced by transcription and replication -number of twists is constant while bps is decreased

Question 39

Supercoiled DNA vs relaxed DNA

Answer 39

-more compact -chromatin for packaging in nucleus

Question 40

DNA of most organisms

Answer 40

negatively supercoiled

Question 41

DNA replication and transcription winding

Answer 41

-overwound ahead of replication fork (positive)