Foundation 1

Question 1

Describe the role of amino acids in forming proteins

Answer 1

Amino acids are the ‘building blocks’ of proteins, they undergo a condensation reaction to form a peptide bond. When many amino acids are in a chain together, that is a polypeptide. Proteins are made up of 10s to 1000s of amino acids (generally 50-2000 amino acids long).

Question 2

Describe how DNA is replicated to produce identical copies

Answer 2

1. Double helix is unwound and the two DNA strands are separated. Done by Helicase.
2. New bases are paired to each strand. Done by DNA polymerase.
3. Double helix reformed and the DNA is checked for errors

Question 3

Describe how gene expression is controlled

Answer 3

1. **Transcriptional regulators (e.g. transcription factors/epigenetic regulators) - switch genes on or off. Activators turn gene expression on, repressors turn gene expression off via action at the enhances, silencers and promoters. Acetylation can turn on expression at the promotor whereas methylation turns off gene expression (these are the epigenetic regulators).
2. RNA processing - alternative splicing, RNA cleavage
3. Nuclear export of mRNA can be regulated - via availability of RNA transport systems and nuclear pores
4. Translational repressors - can bind to the 5’ or 3’ UTR of the mRNA
5. **mRNA half-life depends on function - poly-A tail is degraded over time - acts as a timer, mRNA that is not translated is degraded (e.g. if it has been present without being translated for a while)
6. ** Proteins are activated or inactivated by post-translational modification - e.g. phosphorylation

Question 4

Describe how genetic mutations can result in disease

Answer 4

Genetic mutations lead to changes in the amino acid sequence. When it comes to producing the protein, this will mean that it folds incorrectly, which will have a cellular impact.
For example, the most common genetic mutation associated with cystic fibrosis is ΔF508 (deletion of phenylalanine at position 508) in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein. This causes the protein to misfold and ultimately be ejected by the chaperone in the RER. Hence it doesn’t get expressed on the cell membrane, leading to the symptoms of CF.

Question 5

Describe the genetic code

Answer 5

The genetic code is what determines which protein is codded by a set of 3 nucleotide bases called a codon. 3 bases code for one amino acid or a stop codon.
Important notes:
1. It is a triplet code - 3 nucleotides encode 1 amino acid.
2. The code is non-overlapping - the mRNA is read in discrete groups of 3 nucleotides.
3. The code is redundant -there may be more than one codon for an amino acid (e.g. Serine is UCU, UCC, UCA and UCG).
4. The code is (almost) universal - 61 codons specify amino acids, 3 specify STOP codons (UAA, UAG, UGA). AUG is for methionine (Met) and is the START codon.

Question 6

Describe the organisation of the human genome

Answer 6

There are 23 pairs of chromosomes (46 in total). Half are inherited from mother, half from father. The chromosomes are numbered 1-22 and then XX or XY.
This is not the case in the haploid cells (sex cells - sperm and egg). These have 23 chromosomes because they combine in fertilisation to give the full 46.
The human genome contains ~6 billion base pairs of DNA, but ~1% of this encodes genes.
There are ~30,000 genes in the human genome (nucleus) and there are an additional 37 genes in the mitochondrial genome.
The rest of the genome is made up of non-coding DNA. A lot of this ‘junk’ DNA is actually for regulation - non-coding RNAs (siRNA and miRNA), gene control regions (regions outside of the gene that control expression of the gene) + other functions we don’t know yet.

Question 7

Describe the post-transcriptional processing of RNA

Answer 7

1. 5’ capping - regulates nuclear export, prevents degradation of the 5’ end of the RNA by exonucleases, promotes translation. It also allows the cell to distinguish different types of RNA (mature mRNA)
2. RNA splicing - removes introns to leave the protein coding sequence. When the introns are removed, the RNA can be spliced differently, which can lead to slightly different variations of the protein depending on which combination of exons are splice into the final mRNA.
3. Polyadenylation - addition of the Poly-A tail (~200 nucleotides added to the 3’ end of mRNA). Helps with stabilisation of the mRNA - it prevents degradation of the mRNA’s actual coding sequence because the Poly-A tail can be degraded without consequences. It also allows export from the nucleus (the nucleus can detect that the mRNA is mature when it has the Poly-A tail and 5’ cap).