Mutations and Repair Flashcards
What usually results in mutation?
Failure to repair/repair accurately lesions to the DNA.
Do mutations permanently alter the sequence of bases in a gene?
Yes
What happens where there are mutations in prokaryotes?
The mutation affects only one copy of the genetic information and if the organism survives it will be passed on to the next generation.
Can mutations in germ cells in multicellular organisms be transmitted?
Yes they can to subsequent generations. (I.e. cancer)
What are somatic mutations?
They are mutations that affect tissues (cancer) but are not heritable.
How do eukaryotic cells react when there is damage to DNA?
The cell cycle arrests until repairs are completed. If too extensive apoptosis may be triggered. Tissue damage safer than risk of cancer.
How do prokaryotes react to DNA damage?
Cell cycle arrests and is followed by emergency repair via SOS systems. Many cells die but some mutants survive because cannot afford to lose entire population.
When are somatic mutations harmful?
If they result in a substantial clone of mutant cells (i.e. tumor or mutation in embryogenesis at progenitor cells)
Why do we get cancer?
Some mutations increase mutation rate
Some mutations enhance cell proliferation
What are the four major types of mutation?
Substitution
Deletion
Insertion
Rearrangement
Do mutations tend to occur together or apart?
Deletion, Insertion and Rearrangements tend to occur together (i.e. radiation)
What are the types of substitution mutations?
Silent
Missense
Nonsense
Frameshift
Transition vs. Transversion Substitutions
Transition = purine for purine/pyrimidine for pyrimidine Transversion = purine for pyrimidine/pyrimidine for purine
What is the most common mutation in cystic fibrosis?
Deletion of one codon (Phe out 1480)
What are 4 causes of mutations?
1) Errors during DNA replication (substitutions)
2) Chemical modification (substitutions)
3) Intercalation of certain chemical mutagens between cases (insertions and deletions)
4) Double stranded breakage and “emergency repair” (rearrangements and deletions)
What is intercalation?
Distorts helix which can block DNA replication and RNA transcription
Believed to interfere with any ongoing repair
How does radiation cause mutations?
X-ray exposure causes double stand breaks in DNA resulting in rearrangements and deletions
UV exposure causes thymine dimers that interfere with replication
What does mismatch repair do?
Repairs mismatches
What does base-excision repair do?
Repairs abnormal bases, alkylated bases and pyrimidine dimers
What does nucleotide-excision repair?
DNA lesions that cause large structural changes
What does direct repair repair?
Pyrimidine dimers
How is the correct strand chosen in mismatch repair?
In prokaryotes DNA is methylated at GATC sites which provides a temporary tag for parent strand as replication fork passes through
This guide excision of the daughter instead of the parent strand
What do mismatch repair defects lead too?
Leads to a strong predisposition to cancer (i.e. hereditary nonpolyopsis colorectal cancer)
What enzyme do all cells have that remove abnormal bases in a DNA strand?
DNA glycosylases
How does base excision repair work?
Enzymes remove base but leave sugar intact creating an AP site > specific AP endonuclease cuts sugar out > repair system fills in gap
How does nucleotide excision repair work?
Bulky distortions (thymine dimers) are removed (by ABC exonuclease in E. coli) then repair system fills the gap
What happens in nucleotide excision repair defects?
Leads to an autosomal recessive disease Xeroderma pigmentosum
What are the symptoms of xeroderma pigmentosum?
High sensitivity to skin damage by UV light
Strong predisposition to skin cancer
What happens in infancy with xeroderma pigmentosum?
Skin becomes dry and dermis atrophies
Keratoses form, eyelids scar and cornea ulcerates
Multiple skin tumors form and many patients die before the age of 30 from metastasis
How does direct repair work?
Repair without removing a base or nucleotide Energetically expensive (dealkylating alkylated bases)
Example of low energy cost direct repair
Pyrimidine dimers can be repaired by light induced reverse reaction catalyzed by photolyases (less cost, no chance for more mistakes)
What alkylation agent should you know?
Mustard gas
What is the phenotype of Hereditary nonpolyopsis colorectal cancer?
Colon cancer
What repair process is affected in hereditary nonpolyopsis colorectal cancer?
Mismatch repair
What repair process is affected in zeroderma pigmentosum?
Nucleotide excision-repair
