Errors in DNA replication Flashcards
What is DNA replication stress?
Inefficient replication
leads to replication fork slowing down, stopping or breaking
What are the causes of DNA replication stress?
Defects in enzymes involved
Defects in DNA template strand
Defects in DNA repair pathways
What are some examples of defects in DNA template strand?
Transcription occurring during DNA replication
Ribonucleotide included
DNA lesions
What are some examples of DNA replication errors caused by defects in enzymes involved?
Slippage
Nucleotide misincorporation
What happens in slippage?
Either the template DNA strand or the new DNA strand loops out
What is the consequence of slippage?
New DNA strand is either missing a base
or has an extra base
Which increases the risk of slippage?
Repeated base
What is nucleotide misincorporation?
Incorrect base added to new DNA strand
not complementary
What is responsible for removing mismatched bases?
3’ to 5’ exonuclease
What causes nucleotide misincorporation?
Defects in 3’ to 5’ exonuclease
What are the types of DNA strand breaks?
Single-strand breaks
Double-strand breaks
What is responsible for repairing single-strand breaks?
Base-excision repair
What causes single-strand breaks to persist?
Defect in base-excision repair
What causes double-strand breaks? How?
Single-strand breaks followed by DNA replication
Replication fork reaches break
newly formed DNA molecule breaks off as double-strand
What are the consequences of double-strand breaks in DNA?
Lead to translocation mutations
cell death
disease
What do DNA mutations lead to?
Cancer
What does cell growth inhibition lead to?
Ageing
What is the cause of Huntington’s disease?
Increased number of trinucleotide CAG repeats in Huntington’s gene
produces a protein that gives neurodegeneration
What causes the increased number of CAG repeats in Huntington’s disease?
Slippage
How is Huntington’s disease inherited?
Autosomal dominant
What does the number of CAG repeats in Huntington’s disease relate to?
The age of onset - more CAG repeats means earlier age of onset
What is the multi-step cancer model?
Refers to how an accumulation of mutations is required to cause cancer
What is the cause of Werner syndrome?
Mutations in the Werner gene
leads to defects in helicase, DNA replication
DNA damage
What does the Werner gene code for?
Helicase enzyme involved in DNA replication
How is Werner syndrome inherited?
Autosomal recessive
What is the main symptom of Werner syndrome?
Premature ageing
