DNA damage I & II
Learning objectives:
1. DNA mutation: types & causes
2. Types of DNA damage
3. Examples of diseases associated with mutation
DNA damage: how bad is it?
• Damage to DNA occurs continuously
• In humans, approx. 500,000 modification occur per cell per day
• It is minimised by several different DNA repair systems (>130 repair genes)
LO2. TYPES OF DNA DAMAGE
How does DNA damage occur?
• Endogenous Agents:
- Formed inside the cell by normal metabolic pathways
- i.e. cellular metabolism, which produces oxygen free radicals that damage DNA
• Exogenous agents:
- Come from the surrounding environment
Consequence of DNA damage
• DNA mutation
- Change in DNA sequence element- altered function i.e. promotor, enhancer, transcription factor binding sites
etc
- Change in MRNA sequence that can lead to change in protein sequence
• Mitochondrial DNA can also be damaged
• In a healthy cell
- Rate of DNA damage= rate of repair
• In a diseased cell
- Rate of DNA damage > rate of repair
• Most DNA repair has to take place before DNA replication (i.e. mitosis)
- If DNA is not repaired before mitosis both daughter cell will also contain the mutation
,• Exons occupy 1.2% of human genome
- Means that 98% of the human genome can be mutated without affecting protein
• Additional DNA has regulatory function
- Mutation in i.e. promoter will have an indirect effect and lead to dysregulated transcription, which causes
cancer.
LO1. DNA MUTATION: TYPES & CAUSES
Mutation
• Mutation refers to a heritable change in the genetic material
• Mutation provides allelic variation
• On the positive side
- Mutations are the foundation for evolutionary change needed for species to adapt to changes in the
environment
• On the negative side
- New mutations are much more likely to be harmful than beneficial to the individual and often the causes of
diseases
• Mutations can occur in germ cells or somatic cells
- Germ-line mutation
Occur directly in sperm or egg cell or in one of their precursor cells
All the cells in the human body (somatic and gametes) carry the mutation as all the cell in the body come
from germ cells
Passed on to future generations
- Somatic mutation
Occur in body cells or in its precursor cells (embryo cells)
Cannot be passed on to future generations
, Consequences of mutation
• Mutations can be divided into 3 main types:
1. Chromosomal mutation (polyploidy)
- Changes in chromosome structure
2. Genome mutation
- Changes in chromosome number
3. Gene mutation
- Relatively small change in DNA sequence that affects a single gene
Gene mutations change the DNA sequence
• Point mutation
- Simplest type of mutation
- Change in a single base pair
- Can involve base substitution
• Transition
- Is a change in the pyrimidine to another pyrimidine
C to T
T to C
- Purine to another purine
A to G
Learning objectives:
1. DNA mutation: types & causes
2. Types of DNA damage
3. Examples of diseases associated with mutation
DNA damage: how bad is it?
• Damage to DNA occurs continuously
• In humans, approx. 500,000 modification occur per cell per day
• It is minimised by several different DNA repair systems (>130 repair genes)
LO2. TYPES OF DNA DAMAGE
How does DNA damage occur?
• Endogenous Agents:
- Formed inside the cell by normal metabolic pathways
- i.e. cellular metabolism, which produces oxygen free radicals that damage DNA
• Exogenous agents:
- Come from the surrounding environment
Consequence of DNA damage
• DNA mutation
- Change in DNA sequence element- altered function i.e. promotor, enhancer, transcription factor binding sites
etc
- Change in MRNA sequence that can lead to change in protein sequence
• Mitochondrial DNA can also be damaged
• In a healthy cell
- Rate of DNA damage= rate of repair
• In a diseased cell
- Rate of DNA damage > rate of repair
• Most DNA repair has to take place before DNA replication (i.e. mitosis)
- If DNA is not repaired before mitosis both daughter cell will also contain the mutation
,• Exons occupy 1.2% of human genome
- Means that 98% of the human genome can be mutated without affecting protein
• Additional DNA has regulatory function
- Mutation in i.e. promoter will have an indirect effect and lead to dysregulated transcription, which causes
cancer.
LO1. DNA MUTATION: TYPES & CAUSES
Mutation
• Mutation refers to a heritable change in the genetic material
• Mutation provides allelic variation
• On the positive side
- Mutations are the foundation for evolutionary change needed for species to adapt to changes in the
environment
• On the negative side
- New mutations are much more likely to be harmful than beneficial to the individual and often the causes of
diseases
• Mutations can occur in germ cells or somatic cells
- Germ-line mutation
Occur directly in sperm or egg cell or in one of their precursor cells
All the cells in the human body (somatic and gametes) carry the mutation as all the cell in the body come
from germ cells
Passed on to future generations
- Somatic mutation
Occur in body cells or in its precursor cells (embryo cells)
Cannot be passed on to future generations
, Consequences of mutation
• Mutations can be divided into 3 main types:
1. Chromosomal mutation (polyploidy)
- Changes in chromosome structure
2. Genome mutation
- Changes in chromosome number
3. Gene mutation
- Relatively small change in DNA sequence that affects a single gene
Gene mutations change the DNA sequence
• Point mutation
- Simplest type of mutation
- Change in a single base pair
- Can involve base substitution
• Transition
- Is a change in the pyrimidine to another pyrimidine
C to T
T to C
- Purine to another purine
A to G
