Flashcards in Errors In DNA Replication Deck (13):
What is DNA replication stress?
Inefficient replication that leads to replication fork slowing, stalling or breakage
When does DNA replication stress arise?
When replication machinery has a defect e.g. Helicase stalls
When factors hinder replication fork progression e.g. DNA lesions or repetitive DNA
When there are defects in response pathways e.g. Repair DNA damage tolerances or helicases
What is slippage?
When a newly synthesised strand slips out causing a small loop
This causes one nucleotide extra on the new strand
When template strand loops out, one nucleotide is omitted on the new strand
What is nucleotide misincorporation?
Incorrect nucleotide binds
This is removed by 3' to 5' DNA exonuclease
What causes a DNA single strand break?
Base excision repair defect
Why are double strand breaks the most dangerous type of DNA damage?
Disrupt molecular continuity
Difficult to resolve
If not repaired correctly leaders to mutations or cell death
Types of mutations include translocations and chromothripsis
Arise during DNA replication stress
Lead to cancer and ageing
What can mutations and cell death cause?
What is the cause of Huntington's disease?
Triplet of CAG is repeated 35-121 times rather than 6-39
Disrupts normal function of neurones
Leads to neurodegeneration, death 15-20 years after onset
More repeats, onset sooner
What are the symptoms of Huntington's disease?
Small involuntary movements
Trouble speaking and swallowing
What is the multi step cancer model?
Normal, mutation, mutation, premalignant, mutation, mutation, malignant
Each mutation is a DNA replication stress
What explains why age is the biggest risk factor for cancer?
What occurs in Werner syndrome?
WRN gene is mutated- a helicase that is important in DNA replication
DNA replication defects and DNA damage