Module 6: Cellular control Flashcards
What is a gene mutation?
Change in DNA base sequence that may result in an altered polypeptide. A mutagen (an agent like UV) can increase the risk of mutations.
Examples of mutagens that can cause mutations.
=> Ionising radiation like X-rays can break and damage the DNA sequence.
=> Viruses can insert sections of viral DNA into body cell DNA.
How come most mutations have no effect on us?
Most mutations don’t alter the polypeptide or only slightly so the structure/function is unchanged - genetic code is degenerate (several triplets code for the same amino acid).
Most mutations occur in non-coding sections so have no effect on the amino acid sequence.
How can mutations affect enzymes?
Tertiary structure of protein is changed is the shape of the active site may change, so the substrate may no longer be able to bind.
Name the 3 ways a mutation in a DNA base sequence can occur.
- Insertion of 1 or more nucleotides.
- Deletion of 1 or more nucleotides.
- Substitution of 1 or more nucleotides.
Describe how insertion of a nucleotide (with a new base) works.
An insertion mutation creates new different base triplets so therefore new amino acids. This type of mutation has a knock-on effect by changing the triplets further on in the DNA sequence => FRAMESHIFT mutation. Therefore the ability of the polypeptide to function will change.
Describe how deletion of nucleotides work.
When a nucleotide (and its base) is randomly deleted from the DNA sequence. Also has a knock-on effect by changing the triplets further on in the sequence. FRAMESHIFT mutation.
Describe how substitution of nucleotides work.
A base in the base sequence is randomly swapped for a different base. It doesn’t have a knock-on effect.
Explain the 3 types of substitution mutations.
- Silent mutations - doesn’t alter the amino acid sequence of the polypeptide (genetic code is degenerate).
- Missense mutations - alters a single amino acid in the polypeptide chain (e.g. sickle cell anaemia).
- Nonsense mutations - creates a premature stop codon (signal to stop translation of mRNA into an amino acid sequence). This causes an incomplete polypeptide and will affect overall function (e.g. cystic fibrosis).
Gene mutations can be split into what 3 categories?
Beneficial mutations
Harmful mutations
Neutral mutations
Example of a beneficial mutation.
Antibiotic resistance in bacteria, mosquitoes resistant against insect repellent.
Are all genes expressed in the body?
No, there are regulatory mechanisms that control which genes are expressed at different points in time.
What are the 4 types of regulatory mechanism?
- Transcriptional level - genes can be turned on or off.
- Post-transcriptional level - mRNA is modified which regulates translation and types of protein produced.
- Translational - translation can be stopped or started.
- Post translational level - proteins can be modified after synthesis which changes their functions.
These 4 regulatory mechanisms are controlled by many different regulatory genes.
What is an operon?
A group of genes controlled by a single promoter and are expressed at the same time. Operons are more common in prokaryotes due to their smaller simpler structure.
Describe the structure of the operon.
Promoter – DNA sequence where RNA polymerase binds to start transcription.
Operator – A regulatory sequence where a repressor protein may bind to inhibit transcription.
Structural genes – the actual genes that code for proteins.
Regulatory gene – codes for a repressor or activator protein that controls the operon.
What is lac operon of E.coli?
A group of 3 genes (lacZ, lacY, lacA) involved in the metabolism of lactose and controls production of the enzyme lactase. They are structural genes as they code for 3 enzymes (Beta galactosidase, lactose permease, transacetylase) and they are transcribed onto a single long molecule of DNA.
It’s expressed when lactose is present and glucose is absent.
Lactase is an inducible enzyme - only synthesised when lactose is present. This helps bacteria to not waste energy and materials.
What is a regulatory gene and where is it located on the lac operon?
LacI is located near the operon and codes for a repressor protein that prevents the transcription of structural genes in the absence of lactose.
If the structural gene is controlled during transcription …
The gene control is occuring at the transcriptional level.
Describe the function of the lac repressor protein.
It has 2 binding sites that allow it to bind to the operator on the lac operon and also to lactose.
When it binds to the operator, it prevents transcription of the structural genes as RNA polymerase cannot attach to the promoter.
When it binds to lactose, the shape of the repressor protein distorts and it can no longer bind to the operator.
Describe the 3 structural genes the lac operon consists of.
- lacZ codes for lactase
- lacY codes for permease (allows lactose into the cell)
- lacA codes for transacetylase.
Explain what happens in the lac operon when lactose is ABSENT.
- Regulatory gene is transcribed and translated to produce the lac repressor protein.
- Lac repressor protein binds to the operator region.
- RNA polymerase can’t bind to promoter so no transcription of structural genes.
- No lactase enzyme is made.
Explain what happens in the lac operon when lactose is PRESENT.
- Uptake of lactose by bacterium.
- Lactose binds to the (second binding site of) repressor protein and distorts its shape so it can no longer bind to the operator region.
- RNA polymerase CAN bind to the promoter region and structural genes are transcribed.
- Therefore enzyme lactase is produced and lactose can be broken down and used for energy by the bacterium.
What are transcription factors in eukaryotes?
Proteins that bind to promoters to control transcription. 2 types of transcription factors:
Repressors
Activators
Within eukaryotic genes, there are both coding and non-coding sequences of DNA. What is the difference?
Coding sequences are called exons and will be TRANSLATED into amino acids.
Non-coding sequences are called introns and are not TRANSLATED (they do not code for any amino acids).
Describe what happens during post-transcriptional level.
=> When transcription occurs, both exons and introns are transcribed. So the mRNA contains exons and introns.
=> Splicing occurs where introns are removed and the exons fuse together to form mature mRNA that is ready to be translated.
A cap is added to the 5’ end and tail at the 3’ end. It stabilises the mRNA and delay degradation in the cytoplasm. The cap also aids binding of mRNA to ribosomes.
Also RNA editing through changing the nucleotide sequence in the same way as mutations. They result in the synthesis of different proteins, so have different functions.
Describe translational control.
Degradation of mRNA, binding of inhibitory proteins to mRNA to prevent it binding to ribosomes, activation of initiation factors which aid the binding of mRNA to ribosomes.
Describe post-translational level and cyclic AMP.
Once we have the protein, it undergoes modifications in the Golgi apparatus. This can include the addition of non-protein groups like lipids. Modifying amino acids and its bonds such as disulphide bridges.
Some polypeptides may require activation by cyclic AMP. In the lac operon, cAMP binds to cAMP receptor protein, increasing the rate of transcription of structural genes.
cAMP is derived from ATP and is formed by the action of the enzyme adenyl cyclase.
One important role carried out by cAMP is the activation of protein kinases. In eukaryotic cells, cAMP activates protein kinase A, which is an inactive precursor enzyme.
Protein kinases are enzymes that catalyse the addition of phosphate groups to proteins. This changes the tertiary structure , either activating or deactivating the protein.
Once it is activated, it can activate other proteins (e.g. other enzymes). For example, when muscle cells require energy, an enzyme called glycogen phosphorylase releases glucose from glycogen. This enzyme is activated by cAMP, which changes the shape of the enzyme to expose its active site.
Define homeobox gene.
A gene that contains a homeobox (DNA sequence). These code for homeodomains, which act as transcription factors, so they regulate the expression of genes.
What are homeobox genes responsible for?
They play a crucial role in embryonic development by forming the basic structure of the body and segmentation of body parts and what organs.
Anterior-posterior axis, limb formation, organ development.
What are Hox genes?
Subset of homeobox genes. They determine the body plan of an embryo along the head-to-tail axis.
What is cell apoptosis?
Programmed cell death.
Why is apoptosis important?
Eliminates unwanted cells and cells with damaged DNA so they don’t divide and lead to cancer.
Which 2 groups of genes control mitosis?
- Proto-oncogenes stimulate cell division.
- Tumour-suppressor genes reduce cell division and stimulate apoptosis.
How are the checkpoints in mitosis controlled?
Regulated by 2 groups of proteins called cyclins and cyclin-dependent kinases.
=> Cyclins are regulators that are produced. These stimulate the CDK’s to act as catalysts and have a particular effect.
