Errors In DNA Replication

Question 1

What is DNA replication stress?

Answer 1

Inefficient replication that leads to replication fork slowing, stalling or breakage

Question 2

When does DNA replication stress arise?

Answer 2

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

Question 3

What is slippage?

Answer 3

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

Question 4

What is nucleotide misincorporation?

Answer 4

Incorrect nucleotide binds

This is removed by 3’ to 5’ DNA exonuclease

Question 5

What causes a DNA single strand break?

Answer 5

Base excision repair defect

Question 6

Why are double strand breaks the most dangerous type of DNA damage?

Answer 6

Disrupt molecular continuity
Difficult to resolve
If not repaired correctly leaders to mutations or cell death
Types of mutations include translocations and chromothripsis
Causes disease
Arise during DNA replication stress
Lead to cancer and ageing

Question 7

What can mutations and cell death cause?

Answer 7

Disease

Question 8

What is the cause of Huntington’s disease?

Answer 8

Triplet of CAG is repeated 35-121 times rather than 6-39
Disrupts normal function of neurones
Autosomal dominant
Leads to neurodegeneration, death 15-20 years after onset
More repeats, onset sooner

Question 9

What are the symptoms of Huntington’s disease?

Answer 9

Irritability
Depression
Small involuntary movements
Poor coordination
Decision making
Twitching
Trouble speaking and swallowing

Question 10

What is the multi step cancer model?

Answer 10

Normal, mutation, mutation, premalignant, mutation, mutation, malignant

Each mutation is a DNA replication stress

Question 11

What explains why age is the biggest risk factor for cancer?

Answer 11

Mutation accumulation

Question 12

What occurs in Werner syndrome?

Answer 12

WRN gene is mutated- a helicase that is important in DNA replication
DNA replication defects and DNA damage
Autosomal recessive

Question 13

What are the symptoms of Werner syndrome?

Answer 13

Patients prematurely display features associated with old age
E.g. Cataracts, skin ulcers, type 2 diabetes, atherosclerosis, osteoporosis, cancer