DNA repair & cancer Part 1 Flashcards
What is Ataxia telangiectasia
Ataxia telangiectasia is a rare, neurodegenerative disease that causes severe disability
What are the symptoms of Ataxia telangiectasia
Symptoms include
Damage to the cerebellum leads to difficulty with movement and co-ordination
Weakened immune system and radiation sensitivity
DNA repair is disrupted, heightened cancer risk
When does Damaged DNA lead to a mutation
- If damage is too BIG
- If DNA repair mechanism is faulty
What are the two types of DNA damage
Single stranded Damage
Double stranded damage
Why is double stranded DNA more difficult to repair
Double Stranded DNA is more difficult to repair as in single arm damage, the opposite half of the strand can be used as a template to repair the lesions
What are the Exogenous sources of DNA damage
Ionising radiation
Alkylating agents (adds alkyl group, prevents correct bonding causing breakage of strands)
Mutagenic chemicals
Anti-cancer drugs
Free radicals
How does ionising radiation cause DNA damage
Subatomic particles or electromagnetic waves that have sufficient energy to ionise atoms or molecules by detaching electrons from them
What is the major source of ionising radiation we are exposed to
Major sources include radon gas from ground -50%
and medical procedures.- 15%
is any amount of radiation dangerous
Body’s repair mechanisms can withstand certain amounts of radiation
What is DNA replication stress
Inefficient replication that leads to replication fork slowing, stalling and/or breakage
Defects can occur in the replication machinery
How does Proof reading of base pairs occur
5’ to 3’ DNA polymerase
The wrong base pair is included in copied strand due to error by DNA polymerase
Mismatch removed by 3’ to 5’ DNA exonuclease
(Moves in opposite direction)
DNA exonuclease removes all base pairs until error
5’ to 3’ DNA polymerase recompletes work correctly
What can lead to errors in DNA replication
Limiting nucleotides, DNA lesions, ribonucleotide incorporation, repetitive DNA elements, transcription complexes, DNA secondary structure, fragile sites and oncogene-induced stress
How does repetitive DNA sequence lead to fork slippage
(copy wrong number of repetative sequence)
Large number of a specific base pairs
DNA polymerase finds it hard to accurately copy these thus may add extra base pairs mistakingly
This can lead to slippage and expansion in the size of the gene
This can lead to Huntington’s disease
What is Huntington’s disease
What does Polyglutamine repeats do
Degeneration of the basal ganglia in HD
- Huntington’s disease can be caused by replication errors
- CAG – polyglutamine – repeats in protein
- Repeats much more likely to be miscopied
- Healthy gene has 10-26 repeats
- hunting’s decease gene has 37 - 80 repeats
Huntington’s disease is a condition that stops parts of the brain working properly over time. It’s passed on (inherited) from a person’s parents.
Polyglutamine repeats cause neural degeneration
Progressive, late onset disease – genetic counselling regarding having children
Normal protein function still unknown
Mutant protein aggregates in basal ganglia neurons (movement disorder)
What is the DNA damage response
- DNA damage or Replication stress
- This creates a signal
- Sensor picks up the signal
- this activates downstream pathways the transducers
- This signals effectors to commence
- In most cases DNA is repaired
- Sometimes there is Novel or de novo transcription of damaged genes
if damages is severe
- apoptosis (cell death)
- cell cycle transitions
What is a transducer
A transducer is a device that receives energy from one system and transmits it, often in a different form, to another.
Cell cycle exit and G0
Some types of cells divide rapidly, and in these cases, the daughter cells may immediately undergo another round of cell division. For instance, many cell types in an early embryo divide rapidly, and so do cells in a tumor.
Other types of cells divide slowly or not at all. These cells may exit the G1 phase and enter a resting state called G0
Here the cell isn’t actively preparing to divide, its just doing it job.
What is the G1 phase
Cell grows larger
copies organelles, and makes the molecular building blocks that will be needed in later steps
What is the S phase
In S phase, the cell synthesizes a complete copy of the DNA in its nucleus. It also duplicates a microtubule-organizing structure called the centrosome. The centrosomes help separate DNA during M phase.
What is the G2 phase
the cell grows more, makes proteins and organelles, and begins to reorganize its contents in preparation for mitosis.
G2 ends when when mitosis begins.
What is interphase
G1, S and G2 phases together are known as interphase.
What is the M phase
During the mitotic (M) phase, the cell divides its copied DNA and cytoplasm to make two new cells. M phase involves two distinct division-related processes: mitosis and cytokinesis.
What is mitosis
In mitosis, the nuclear DNA of the cell condenses into visible chromosomes and is pulled apart by the mitotic spindle, a specialized structure made out of microtubules. Mitosis takes place in four stages: prophase (sometimes divided into early prophase and prometaphase), metaphase, anaphase, and telophase.
What is cytokinesis
In cytokinesis, the cytoplasm of the cell is split in two, making two new cells. Cytokinesis usually begins just as mitosis is ending, with a little overlap. Importantly, cytokinesis takes place differently in animal and plant cells.
