Prof C. Smythe Flashcards
What does a nucleus do?
Separates the process of transcription and translation which allows for regulation (splicing)
What are 2 possible origins of the nucleus?
- Invagination of membrane around DNA
- Prokaryote was engulfed by another and formed a symbiotic relationship (endosymbiosis)
What are the features of the nuclear envelope? (4)
- Double membrane
- Nuclear pores
- Continuity between outer membrane and endoplasmic reticulum
- Outer membrane has ribosomes
How is DNA packaged inside the nucleus?
Wrapped around histones
What is a nucleosome?
Structural unit of DNA wrapped around a histone
What is heterochromatin?
Tightly packed condensed DNA around periphery of nucleus, transcription is suppressed
What is euchromatin?
Less condensed DNA in the larger volume of the nucleus, more active in transcription
What are chromosome territories?
Inherited location of genes in the nucleus which changes depending on the transcriptional status of the gene
Where are chromosomes located when they are being expressed?
Euchromatic region
What happens in the nucleolus?
- Contains ribosomal RNA for ribosome synthesis
- Not membrane bound
What is the function of speckles?
Pre-mRNA processing
What is the function of Cajal bodies?
Splicing
What is the function of PML bodies?
Storage depots
What is the nuclear lamina?
Fibrous meshwork which provides structural support to the nuclear envelope made of intermediate filaments and other proteins.
What are the functions of the lamina?
- Ensures asymmetric nature of nuclear membrane
- Acts as an anchor for membrane proteins on the inner membrane which aren’t present on the outer membrane
What is present on the outer membrane of the nuclear envelope?
Ribosomes
How are the inner and outer nuclear membranes connected?
Nuclear pores
What disease is caused by a mutation in the nuclear lamina?
Progeria
How do particles enter the nucleus which are too big to diffuse through nuclear pores?
Signal-dependent transport where the signal is a specific peptide sequence
What is the function of the nuclear pore?
Regulates the movement of substances in and out of the nucleus
What does dysplastic mean?
Abnormal
What can cause cancer?
- Environmental factors
- Genetic predispositions
What are examples of environmental causes of cancer?
- Infection
- Diet
- Noxious agents
Which cell behaviours are disrupted by cancers?
- Cell proliferation
- Cell adhesion
- Cell mobility
What is a protein kinase?
Enzymes which take a phosphate from ATP and add it onto a specific site on a target protein which then changes its activity (on/off switch)
What is an oncogene?
- A gene with the potential to cause cancer by transforming cell behaviour
- Genetically dominant
What is a proto-oncogene?
A gene involved in regulated cell proliferation that can become an oncogene and cause cancer if mutated (activated)
How do viruses cause cancer?
They contain an oncogene
Making cells proliferate is advantageous for the virus-make more host cells for virus replication
What is an example of a proto-oncogene?
Ras
What is the Ras protein?
GTPase
How does the Ras protein work?
- Bound to GTP= switched on
- Bound to GDP= switched off
- When switched on it encourages cell proliferation
- Exchange factors can switch it on by exchanging GDP for GTP
How can Ras cause cancer?
Mutations cause Ras proteins to be permanently switched on (activated) so don’t respond to growth factors and cause unregulated proliferation
What is a tumour suppressor gene?
A gene which regulates normal cell division
What are the features of oncogenes?
- Needs to be ACTIVATED from a proto-oncogene
- Are DOMINANT
- Mutation causes INCREASED function of its protein product
What are the features of tumour suppressor genes?
- Needs to be INACTIVATED
- Are RECESSIVE (both alleles must be mutated)
- Mutation causes DECREASED function of its protein product
What are examples of tumour suppressor genes?
- Rb
- p53
How do inherited tumour suppressor gene mutations cause cancer?
Individuals inherit one mutated allele so only one mutation needs to be acquired in the other copy of the tumour suppressor gene in order for both forms to be knocked out which then causes cancer
(Two hit hypothesis)
What causes inherited forms of cancer?
Heritable mutations in tumour suppressor genes
What are the causes of genetic instability in cancer cells?
Defects in:
- DNA repair pathways
- Correction mechanisms for DNA replication errors
- Correction mechanisms for DNA segregation errors
How do tumour suppressor mutations lead to cancer?
- Loss of regulated cell division so mutated cell proliferates more than those around it
- More cells=more likely to develop random mutations
- Accumulation of many mutations over time leads to cancer (evolutionary disease)
What is a normal cell’s response to cellular stressors?
Apoptosis
Which gene is switched on in response to cellular stressors?
p53
What stressors cause activation of p53?
- Hypoxia
- DNA damage
- High signalling levels
- Carcinogens
- Telomere shortening
What does activated p53 do?
- Cell cycle arrest
- Senescence
- Apoptosis
What is senescence?
When a cell permanently stops dividing but doesn’t die
How does p53 mutation lead to cancer?
A mutation causes the p53 to be inactive which causes a disruption in apoptosis so proliferation is not regulated and DNA damage can accumulate in cells.
At which checkpoints in the cell cycle does p53 act?
G1/S and G2/M checkpoints
Where in the cell cycle does Rb act?
Rb can stop the cell cycle at the restriction point at the end of G1 (not strictly a checkpoint)
How does a mutation in Rb lead to cancer?
Lack of Rb means the cell cycle can’t be stopped at the restriction point which leads to unregulated proliferation
