Chapter 2: DNA structure and stability: mutations vs. repair (Lecture 1) Flashcards
What will be discussed in the lecture? (you obv don’t have to know this, just so you know what you can expect)
1) DNA maintenance and cancer.
2) Type of DNA aberrations.
3) Causes of DNA aberrations: exogenous & endogenous.
4) DNA Repair mechanisms: cancer-predisposition syndromes.
5) Cancer therapeutics.
How does a DNA molecule look? (you should be able to identify all structures, but because I deem this basic knowledge, there is only one card about it)
Explain the process of genetic stability and genetic instability
Cancer can result from (epi)genetic alterations in human Cancer Genes. What are the three categories for this?
- Stability genes (e.g. repair)
- Oncogenes (eg growth factors)
- Tumor suppressor genes
note: tumors can also be caused by DNA tumor viruses
Explain for each category of (epi)genetic alterations whether there is activation or inactivation so that cancer can ‘occur’. (1. stability genes, 2. oncogenes, 3. tumor suppressor genes)
- Activation: oncogenes
- Inactivation: stability genes and tumor suppressor genes
Changes in the DNA can be divided into small and larges changes. What are some examples for each group?
- Small changes: Base pair substitutions, deletions or insertions, single- and double-strand breaks.
- Large changes: Changes in DNA content per nucleus, chromosome rearrangements, gene amplifications.
Are all DNA changes oncogenic?
No
What can base pair substitutions (also called point mutation) lead to? (3 answers)
A point mutation may cause a silent mutation if the mRNA codon codes for the same amino acid, a missense mutation if the mRNA codon codes for a different amino acid, or a nonsense mutation if the mRNA codon becomes a stop codon.
What are examples of frameshift mutations?
Insertions and deletions
What can frameshift mutations (insertions/deletions) cause?
A change in the reading frame and/or a premature stop codon
What is more dangerous and why; single strand breaks or double strand breaks?
Double strand breaks because there is a risk for deletions and large chromosome rearrangements. It is also extremely toxic
DNA aberrations can be exogenous or endogenous. What are risk factors for exogenous DNA aberrations?
- smoking: polycyclic aromatic hydrocarbons (PAHs)
- drinking: alcohol
- sun: UV - radiation
DNA aberrations can be exogenous or endogenous. What are risk factors for endogenous DNA aberrations?
- DNA replication mistakes
- reactive oxygen species (ROS)
- Oxidative phosphorylation in the mitochondria produces reactive oxygen species
What type of genetic alteration (by a DNA-damaging agent) is depicted in this figure? What is it caused by?
A pyrimidine dimer caused by UV
What type of genetic alteration (by a DNA-damaging agent) is depicted in this figure? What is it caused by?
Strand break by X-rays
What type of genetic alteration (by a DNA-damaging agent) is depicted in this figure? What is it caused by? add fig
Bulky adduct by PAH
What can cause base loss?
Spontaneous hydrolysis
What type of genetic alteration (by a DNA-damaging agent) is depicted in this figure? What is it caused by?
6-4 photoproduct by UV
(note the difference between a pyrimidine dimer by UV where there’s a double bond between the thymines)
What type of genetic alteration (by a DNA-damaging agent) is depicted in this figure? What is it caused by?
Interstrand crosslink by nitrogen mustard, cisplatin and MMC
What type of genetic alteration (by a DNA-damaging agent) is depicted in this figure? What is it caused by?
Intrastrand adduct by cisplatin
What can a modified base be caused by?
Alkylating agents, such as reactive oxygen
For overview purposes, what are the different genetic alterations induced by DNA-damaging agents?
Oxidative stress can cause 8-oxoguanine. How does this look different from a normal guanine?
As indicated by the red circle and green arrow, an O and N is added
What can 8-oxoguanine be caused by?
Ionizing radiation or normal cellular metabolism (aging)
Why is 8-oxoguanine potentially mutagenic?
Because DNA polymerase reads it as a thymine, (wrong nucleotide -> wrong amino acid -> harmful for the protein)