T1L1/2: DNA and Chromosomes

Question 1

DNA function [3]

Answer 1

Encode all info required to make an organism (DNA to RNA to protein)

Must replicate accurately

Must allow beneficial mutations to be selected

Question 2

Human genome stats [5]

Answer 2

3.2 billion (3,200,000,000) bases of DNA (3.2 x109)

~50% high-copy repetitive elements
1.5% protein coding & 80% functional

20,000-25,000 genes

Question 3

Variation extent [3]

Answer 3

Genes 99.9% identical

Each have ~3 million single nucleotide polymorphisms (SNP)

Each have ~50-100 SNPs associated with an inherited disease.

Question 4

First level of folding: Nucleosome [3]

Answer 4

Core particle

 8 histones (octamer)
		○ (2x) H2A, H2B, H3 and H4
Histones +ve, DNA –ve charged

Question 5

Second level of folding [1]

Answer 5

Involves H1

Question 6

DNA condensation regulation [3]

Answer 6

Chromatin remodelling complexes

Histone-modifying enzymes (acetyl phosphate or methyl groups)

Question 7

Epigenetics

Answer 7

Heritable changes in gene function that cannot be explained by DNA sequence changes

Question 8

Rubinstein-Taybi syndrome (RSTS) [5]

Answer 8

Non-specific symptoms    
Mental retardation
 Facial abnormalities
Broad thumbs and broad great toes
RSTS: mutation in histone acetyl-transferases

Question 9

Chromatin-remodelling complexes:

Answer 9

protein machines which use energy from hydrolysis of ATP to change position of DNA wrapped around nucleosome

Complexes attach to both histone octamer and DNA wrapped around it
Can locally alter arrangement of nucleosomes on DNA -> more accessible

Question 10

Reversible chemical modification of the histones [3]

Answer 10

The tails of all 4 core histones particularly subject to these covalent modifications

Modifications have important consequences for stability of chromatin fibre

Acetylation of lysine reduces affinity of tails for adjacent nucleosomes - loosens structure & allows access to particular nuclear proteins

Question 11

Regulation of chromosome structure

Answer 11

• Modifications can serve as docking sites on histone tails for a variety of regulatory proteins
• Different patterns of modification attract different proteins to particular structure stretches of chromatin
Some proteins promote chromatin condensation & others de-condense chromatin & facilitate access o DNA

Question 12

Interphase chromosomes

Answer 12

• Localised alteration of chromatin packing by remodelling complexes and histone modification has important effects on large-scale structure of interphase chromosomes
  
  • Interphase chromatin is not uniformly packed
  • Most highly condensed form of interphase chromatin is Euchromatin
  • Each chromatin structure is established and maintained by different sets of histone tail modifications which attract distinct sets of non-histone proteins
  • Heterochromatin can spread as histone tail modifications attract a set of heterochromatin-specific proteins - include histone-modifying enzymes which create same histone tails modifications on adjacent nucleosomes
  • This heterochromatin continues to spread until it encounters a barrier DNA sequence that stops propagation
  Most DNA in heterochromatin do not code for anything - so compact some genes are not expressed