Lecture 4 - DNA Structure

Question 1

History of DNA (6)

Answer 1

James Watson and Francis Crick worked out the structure in 1953
Used work from Rosalind Franklin and Maurice Williams to build a model of DNA.
Franklin’s report showed the nitrogenous bases were hidden inside of the DNA.
X-Ray Crystallography showed DNA made up of two strands.

Question 2

Central dogma

Answer 2

DNA makes RNA make so protein

Question 3

Form of DNA (5)

Answer 3

DNA is present as chromatin in the nucleus.
DNA repairs itself
Each strand has polarity
DNA is acidic
When DNA is packaged into chromatin it is attracted to the positive histones.

Question 4

Pyrimidines

Answer 4

Single ringed/smaller bases- Thymine (T) and Cytosine (C).

Question 5

Purines

Answer 5

Double ringed/larger bases– Adenine (A) and Guanine (G).

Question 6

Hydrogen bonds (2)

Answer 6

A and T 1.11 nm.

G and C 1.08 nm.

Question 7

Angstrom

Answer 7

ångström is a unit of length equal to 10−10 m (one ten-billionth of a metre) or 0.1 nanometre. It is used to express sizes of atoms, molecules, microscopic biological structures, and lengths of chemical bonds, arrangement of atoms in crystals, wavelengths of electromagnetic radiation, and dimensions of integrated circuit parts.

Question 8

Features of the Watson-Crick model of DNA deduced from the diffraction patterns (8)

Answer 8

2 polynucleotide strands, antiparallel.
Sugar-phosphate backbone outside, bases inside.
Bases are perpendicular to helix axis.
- Adjacent bases 3.4 A
- Helical structure repeats every 34 A.
- 10.4 bases per turn.
- 36 degrees per base rotation.
- Diameter of helix is 20 A.

Question 9

A DNA (6)

Answer 9

More compact than B DNA.
Major and minor grove are very similar in size.
Wider and shorter than B -form helix.
Base pairs are tilted rather than perpendicular to the helix axis.
tRNA takes this form – A form nucleic acid, this is self-complementary
Major groove is favoured for drugs

Question 10

B DNA (3)

Answer 10

Major groove and minor grove, can be accessed by drugs/proteins to read the sequence of DNA.
Rosalind Franklin found the x-ray diffraction photograph for this type of DNA.
Major 240, Minor 120

Question 11

anti/syn orientation

Answer 11

Syn and anti refer to the orientation of the N-glycosidic bond between the base and deoxyribose. In the anti orientation, the base extends away from the deoxyribose. In the syn orientation, the base is above the deoxyribose. Pyrimidines can be in anti orientations only, whereas purines can be anti or syn.

Question 12

Statistics for A/B/Z

Answer 12

Notes

Question 13

Unusual DNA structure (3)

Answer 13

Left handed/ Z DNA.
Four stranded junction - Holiday junction.
Tetraplex DNA.

Question 14

Four stranded junction - Holiday junction (2) Function (2)

Answer 14

Forms during normal chromosome replication.
Four-way junction involving strand exchange, forms when 2 chromosomes join.
Function
- Homologous recombination
- Double stranded break

Question 15

Tetraplex DNA (3)

Answer 15

Formed at the telomeres (which protect the chromosomes).
Formed by DNA folding back in itself.
Involves G rich sequences.

Question 16

Levels of DNA Structure (4)

Answer 16

Primary – Sequence of bases (found by DNA sequencing). Can be useful when developing drugs/vaccines to target specific enzymes.
Secondary – Helical structure [e.g. A,B,Z] (X –ray crystallography and chemistry).
Tertiary – DNA supercoiling (electron microscopy)
DNA is the nucleus is 2m long, needs to coil to fit.
Quaternary – Interlocked chromosomes [e.g. when bacteria replicate and chromosomes interlock initially].

Question 17

Bacterial DNA

Answer 17

DNA is circular and comprises of 3 x 106 base pairs (around 3 million).
Is supercoiled – in bacteria to replicate, supercoil stores energy.
Caused by the enzyme DNA gyrase (which uses ATP to twist up the DNA like a rubber band which is reversible).
Chromosome is circular and organised into around 50 independently supercoiled domains, with a central domain.

Question 18

DNA in eukaryotic cells (5)

Answer 18

3 billion base pairs of DNA.
DNA is complexed with histones made into chromatin.
DNA double helix wound into 8 histone subunits (2A, 2B, 3 and 4) - histone octate.
Compacting the DNA by a factor of 6. Histone 1 binds to the outside and to linker DNA.

Question 19

Nucleosome

Answer 19

Is the basic building block of chromatin.

Question 20

Folding of nucleosomes (2)

Answer 20

Multiple nucleosomes are coiled together, resulting in a fibre called chromatin, which is then condensed to a 30nm chromatin fibre.
Then looped and coiled more, using other proteins to form the chromosomes, which only form when cells are dividing.

Question 21

DNA damage (6)

Answer 21

Simple mutations.
Deamination --> C to U.
Missing bases .
Strand breaks.
Oxidative stress (radicals).
Ionising radiation.

Question 22

Is DNA stable?

Answer 22

DNA is chemically unstable, it is joined by sugars, whose bonds can be hydrolysed at a finite rate.

Question 23

DNA repair (4)

Answer 23

Direct repair.
Excision repair - Endonuclease cleaves the DNA backbone with the abnormal base and replaces it with the correct base and reformed with DNA ligase.
Mismatch base pair - wrong bases are in the daughter strand so adenine bases are labelled by methyl groups so new replicated DNA is hemimethylated.
Recombination repair - thymine dimerisation so DNA replication can’t work properly.

Question 24

Condition where there is a fault in the repairing mechanism

Answer 24

Xeroderma Pigmentosum

Defect in the excision repair - very prone to skin cancer.