1. We will be studying: DNA Mutations DNA Damage DNA Repair Processes
DNA Damage and Repair
We will be studying:
DNA Mutations
DNA Damage
DNA Repair Processes
Part 1 Lecture Modified from Types of Mutations PowerPoint at
Part 2 Lecture Designed by Claire R. Laquerre – WACTC Biotechnology Program
Laboratory Investigation: EDVO-Kit # 957

2. How and why do these mistakes happen ?
Part I. DNA Mutations
How and why do these mistakes happen ?

3. What Are Mutations? Changes in the nucleotide sequence of DNA
May occur in somatic cells which are not passed to offspring.
May occur in gametes (eggs & sperm) and can be passed to offspring

4. Helpful or Harmful?
Some types of skin cancers and leukemia result from somatic mutations. HARMFUL
But, Some mutations may improve an organism’s chance of survival.
BENEFICIAL

5. How can the DNA Sequence change ?
Types of Mutations
How can the DNA Sequence change ?

6. 1. Chromosome Mutations May Involve:
Changing the structure of the chromosome
loss or gain of a part of a chromosome

7. Chromosome Mutations Five types of Chromosome Mutations Deletion
Duplication
Inversion
Translocation
Nondisjunction

8. Deletion Mutations
A piece of a chromosome is lost
Due to breakage

9. 46 xx 5p- Deletion Example

10. Duplication Mutation
Occurs when a gene sequence is repeated Severity of the error depends if the duplication occurs in an intron or in an exon.
Introns are not translated but exons are translated

11. Inversion Mutations What Happens: Chromosome segment breaks off
Segment flips around backwards
Segment reattaches

12. Translocation Mutations
Involves two chromosomes that aren’t homologous
Part of one chromosome is transferred to another chromosomes

13. SUMMARY

14. Nondisjunction Mutations
Failure of chromosomes to separate during meiosis
Causes gamete to have too many or too few chromosomes

15. Results of Nondisjunction
Linda Hunt Star of NCIS - LA
45 XO
Turner Syndrome

16. Another Example – 47 XXY

17. Chromosome Mutation Summary

18. 2. Gene Mutations Change in the nucleotide sequence of a gene
May only involve a single nucleotide
May be due to copying errors, chemicals, viruses, etc.

19. Types of Gene Mutations
Include:
Point Mutations
Substitutions
Insertions
Deletions
Frameshift

20. Point Mutations Change of a single nucleotide.
Includes the deletion, insertion, or substitution of ONE nucleotide in a gene

21. Frameshift Mutations Inserting or deleting one or more nucleotides
Changes the “reading frame” like changing a sentence
Proteins built incorrectly

22. Frameshift Mutation Original: The fat cat ate the wee rat.
Frame Shift (“a” added):
The fat caa tat eth ewe era t.

23. Frameshift from Insertion
Original Sequence
Point Mutation

24. Frameshift from Deletion

25. Non-frameshift Insertion
Not all insertions result in a frameshift but, most do.

26. Part 2. DNA Damage & Repair
How Does the Cell Fix These Mistakes ?

27. DNA Damage and Repair How Often Do You Think DNA Damage Occurs?
DNA damage occurs at a rate of 10,000 – 1,000,000 molecular lesions per cell per day!
DNA damage resulting in multiple broken chromosomes
Image:
Good News is:
This only affects % of the human genome.
(about 3 billion base pairs)

28. Effect of DNA Damage BUT,
HOWEVER,
If the damage occurs in genes coding for critical proteins, major problems such as:
Cell death
Tumors
Cancer
BUT,
If damage occurs in a tumor suppressor gene, the likelihood of that cell to become cancerous greatly increases.

29. Sources of DNA Damage Endogenous known as spontaneous mutations
There are two main divisions of DNA damage
Endogenous
known as spontaneous mutations
damage is due to products (reactive oxygen species) released during normal metabolic activity.
Also includes replication errors
Exogenous
Damage caused by external agents. Such as:
ultraviolet light nm
x-rays and gamma rays
hydrolysis
thermal disruption
plant toxins
mutagenic chemical
viruses

30. Endogenous Damage Comes from normal cellular processes
Oxidation of nitrogen bases which cause strand interruptions.
Alkylation of nitrogen bases (usually methylation)
Hydrolysis of nitrogen bases
Base mismatches due to errors in DNA replication.
wrong base is inserted
base is skipped
extra base is inserted

31. Point Mutation in a Gene
Sickle Cell disease is the result of one nucleotide substitution
Occurs in the hemoglobin gene

32. 06_19_sickle_cell.jpg
06_19_sickle_cell.jpg

33. A Normal Process to Regulate Gene Expression

35. Exogenous Damage Formation of Cross linkage of bases called Dimers.
comes from outside (environmental agents)
Formation of Cross linkage of bases called Dimers.
Pyrimidine Dimers
thymine bonded to thymine
cytosine bonded to cytosine
Purine Dimers
adenine bonded to adenine
guanine bonded to guanine
This is called direct DNA damage and is caused by UV-B light
Free Radical Formation caused by UV-A light
This damage is called indirect DNA Damage

36. UV-B Light Damage Produces Pyrimidine Dimers
AKA: Thymine Cross bridges
Takes an extreme amount of energy

37. Occurs at elevated temperatures
Exogenous Damage
environmental agents continued . . .
Ionizing Radiation
Radioactive decay
Cosmic rays
Causes breaks in DNA strands which is responsible for transcription errors
Leads to pre-mature aging and cancer
Thermal Disruption
Occurs at elevated temperatures
causes depurination (loss of purine bases)
- rate of depurination is 300 purine disruptions per genome
causes single-strand breaks

38. Exogenous Damage Industrial Chemicals Vinyl chloride
environmental agents continued . . .
Industrial Chemicals
Vinyl chloride
Hydrogen perioxide
Polycyclic aromatic hydrocarbons

39. Exogenous Damage Summary
Environmental Agents
Categorized as
Induced Damage
UV damage
Alkylation/methylation
X-ray damage
Oxidative damage
Categorized as Spontaneous Damage
Loss of a base
Deamination
Sugar Ring Puckering
Tautomeric shift

40. DNA repair rate is an important determinant of cell pathology
DNA Damage
DNA repair rate is an important determinant of cell pathology