S3) DNA Repair & Cancer Flashcards
What is DNA Replication stress?
DNA replication stress is inefficient replication that leads to replication fork slowing, stalling &/or breakage
Identify 3 causes of DNA replication stress
- Replication machinery defects
- Factors hindering replication fork progression
- Defects in response pathways e.g. helicases
Nucleotide misincorporation is a replication machinery defect.
What causes it?
Defects in 3’ to 5’ exonuclease capacity of DNA polymerases
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/214/a_image_thumb.png?1509199963)
Repetitive DNA is a replication fork hindrance.
What causes it?
Replication fork slippage:
- Resulting in insertion
- Resulting in deletion
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/216/a_image_thumb.png?1509200161)
The effects of replication fork slippage can be seen in trinucleotide repeat disorders.
Identify and describe and example of this
Huntington’s disease where triplet repeat expansion leads to neurodegeneration
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/219/a_image_thumb.jpg?1509200312)
What is Huntington’s disease?
Huntington’s disease is an inherited neurodegenerative disease, affecting mostly basal ganglia and leading to the degeneration of voluntary motor functions, procedural learning, routines, cognition and emotions
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/221/a_image_thumb.png?1509200706)
What is significant about the CAG repeats in Huntington’s disease?
- Normal gene: 6–39 repeats
- Disease gene: 35–121 repeats
- Number of repeats is inversely correlated with age of onset
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/225/a_image_thumb.jpg?1509200373)
State the pattern of inheritance of Huntington’s disease
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/231/a_image_thumb.png?1509200458)
Describe the molecular basis for Huntington’s disease
- Mutant protein accumulates and aggregates in neurons
- Mutant protein disrupts various cellular processes & functions, leading to cell dysfunction and death
In Huntington’s disease, death usually occurs 15-20 years after symptoms begin.
Identify 5 symptoms
- Irritability
- Depression
- Small involuntary movements
- Poor coordination
- Difficulties speaking/swallowing
What is the Werner protein?
The Werner protein is a helicase that is important during DNA replication
What is Werner Syndrome?
Werner syndrome is a clinical condition involving mutations in the WRN gene leading to DNA replication defects, DNA damage and ultimately, cell growth defects
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/238/a_image_thumb.jpg?1509201016)
State the pattern of inheritance of Werner Syndrome
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/245/a_image_thumb.jpg?1509201171)
In Werner Syndrome, patients prematurely display features associated with normal ageing.
Identify 5 other symptoms
![](https://s3.amazonaws.com/brainscape-prod/system/cm/513/239/252/q_image_thumb.jpg?1509201224)
- Cataracts
- Skin ulcers
- Type II diabetes
- Atherosclerosis
- Osteoporosis
Identify the two main forms of DNA damage and their resulting effects
- Genomic mutations: Huntington’s disease & cancer
- Cell growth inhibition: ageing