H2 DNA structure and stability: mutations vs
repair
Kataegis = small areas of hypermutation
Chromothripsis = many genomic rearrangements
2.1 gene structure – two parts of a gene: the regulatory
region and the coding region
5’ end of a gene:
- Promoter = regulates the expression of the gene
o TATA box = regulatory elements
TATA box-binding proteint binds to TATA box initiation
transcription
o Response element (RE) = recognized by transcription factors
SRE = serum response element (production of blood serum)
E2F RE = in promoters of cell-cycle genes (cyclin E and A)
- Enhancer = regulatory DNA element, controls tissue/stage specific
expression
2.2 mutations
Transitions = purine purine (eg. A G)
Transversions = purine pyrimidine (eg. A T)
Insertion or deletion can alter the reading frame non functional/
truncated protein
Chromosomal translocation = exchange of one part of one
chromosome for another
Gene amplification = copy number of a gene increases
Driver mutations = cause growth advantage
Mutations in the promoter region may alter gene regulation
2.3 carcinogenic agents
Radiation = energy
- Traveling in waves (gamma rays, X-rays)
- As atomic particles (alpha and beta particles)
Electromagnetic radiation
- Moves as energy waves (wavelengths)
- High energy = short wavelength (gamma rays, X-rays)
- Low energy = long wavelength (radio waves)
- Visible spectrum
- UV radiation (sun)
Radiation can damage DNA carcinogen
High-LET (linear energy transfer)
, - Releases more energy over a distance
- Causes more damage: dsDNA breaks translocations/deletions
Low-LET
- Releases less energy over the same distance
Grays (Gy) = 1joule/kg energy absorbed by tissue
Biological damage measure: Sv = Gy x LET factor
2 major carcinogeneic radiation classes:
1. ionizing radiation
- Leukemia
- alpha and beta particles, gamma rays
Molecules lose electrons form ions
DNA damage:
- Direct ionization of DNA atoms
- Indirect radiolysis of water ROS DNA damage
2. Ultraviolet (UV) radiation
UVB damage (290-320 nm)
- Penetrates into the basal level of the epidermis
- Cyclobutene pyrimidine dimers (CPDs)
o Pyrimidine = T, C
- CPDs distort DNA polymerase adds oppositely with A
o TT dimer AA complementary strand TT new strand
repaired normally
o CC dimer AA complementary strand TT new strand
Wrong repaired; C T transition
UVA damage (320 – 380 nm)
- Penetrates into the dermis (deeper, but acellular; no cells present
only ecm)
- Water fragmentation ROS formation
- G T transversions
fluoroquinolone antibiotics = photosensitized carcinogens; absorb a lot
of UV light
stay out of the sun when using
repair
Kataegis = small areas of hypermutation
Chromothripsis = many genomic rearrangements
2.1 gene structure – two parts of a gene: the regulatory
region and the coding region
5’ end of a gene:
- Promoter = regulates the expression of the gene
o TATA box = regulatory elements
TATA box-binding proteint binds to TATA box initiation
transcription
o Response element (RE) = recognized by transcription factors
SRE = serum response element (production of blood serum)
E2F RE = in promoters of cell-cycle genes (cyclin E and A)
- Enhancer = regulatory DNA element, controls tissue/stage specific
expression
2.2 mutations
Transitions = purine purine (eg. A G)
Transversions = purine pyrimidine (eg. A T)
Insertion or deletion can alter the reading frame non functional/
truncated protein
Chromosomal translocation = exchange of one part of one
chromosome for another
Gene amplification = copy number of a gene increases
Driver mutations = cause growth advantage
Mutations in the promoter region may alter gene regulation
2.3 carcinogenic agents
Radiation = energy
- Traveling in waves (gamma rays, X-rays)
- As atomic particles (alpha and beta particles)
Electromagnetic radiation
- Moves as energy waves (wavelengths)
- High energy = short wavelength (gamma rays, X-rays)
- Low energy = long wavelength (radio waves)
- Visible spectrum
- UV radiation (sun)
Radiation can damage DNA carcinogen
High-LET (linear energy transfer)
, - Releases more energy over a distance
- Causes more damage: dsDNA breaks translocations/deletions
Low-LET
- Releases less energy over the same distance
Grays (Gy) = 1joule/kg energy absorbed by tissue
Biological damage measure: Sv = Gy x LET factor
2 major carcinogeneic radiation classes:
1. ionizing radiation
- Leukemia
- alpha and beta particles, gamma rays
Molecules lose electrons form ions
DNA damage:
- Direct ionization of DNA atoms
- Indirect radiolysis of water ROS DNA damage
2. Ultraviolet (UV) radiation
UVB damage (290-320 nm)
- Penetrates into the basal level of the epidermis
- Cyclobutene pyrimidine dimers (CPDs)
o Pyrimidine = T, C
- CPDs distort DNA polymerase adds oppositely with A
o TT dimer AA complementary strand TT new strand
repaired normally
o CC dimer AA complementary strand TT new strand
Wrong repaired; C T transition
UVA damage (320 – 380 nm)
- Penetrates into the dermis (deeper, but acellular; no cells present
only ecm)
- Water fragmentation ROS formation
- G T transversions
fluoroquinolone antibiotics = photosensitized carcinogens; absorb a lot
of UV light
stay out of the sun when using
