DNA damage, types by kk sahu

Introduction
Defination
What is damage?
Mutation
Types of mutation
Sources of damage
1.Endogenous
2.Exogenous
Types of damage
Common Carcinogen
Conclusion
Reference

1. TYPES OF DNA DAMAGE By KAUSHAL KUMAR SAHU Assistant Professor (Ad Hoc) Department of Biotechnology Govt. Digvijay Autonomous P. G. College Raj-Nandgaon ( C. G. )

2. SYNOPSIS Introduction Defination What is damage? Mutation Types of mutation Sources of damage 1.Endogenous 2.Exogenous Types of damage Common Carcinogen Conclusion Reference

3. INTRODUCTION DNA (Deoxyribose nucleic acid) DNA is a long polymer made from repeating units called nucleotides. As first discovered by James D. Watson and Francis Crick, the structure of DNA of all species comprises two helical chains each coiled round the same axis . STRUCTURE OF DNA - DNA is a very large molecule made up of a long chain of sub-units. The sub-units are called nucleotides . Each nucleotide is made up of a sugar called deoxyribose . a phosphate group -PO 4 and an organic base.

4. Definition DNA damage is an alteration in the chemical structure of DNA such as a break in a strand of DNA a missing form the backbone of DNA or a chemically base.

5. WHAT IS DNA DAMAGE DNA damage is the result of irreversible modification of DNA nucleotides or breakage of DNA strands. Although repair systems can fix minor damage, cell death results if the damage cannot be repaired.

6. Fig- DNA damage

7. MUTATION- Any change in DNA base sequence referred as Mutation. Agent which causes mutation referred as Mutagen. The process through which mutation occurs known as Mutagenesis. Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by mutagens . Spontaneous mutation Spontaneous mutations on the molecular level can be caused by. 1.Tautomerism. 2.Depurination. 3.Deamination. 4.Slipped strand mispairing .

8. Induced mutation Induced mutations on the molecular level can be caused by: Chemicals Hydroxylamine NH 2 O Alkylating agents (e.g. N-ethyl-N-nitrosourea) Agents that form DNA adducts (e.g. Ochratoxin A metabolites) DNA intercalating agents (e.g. Ethidium bromide) DNA crosslinkers Oxidative damage

9. By effect on structure Point mutations , often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide  from another. These changes are classified as transitions or transversions . Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements. Deletions  of large chromosomal regions, leading to loss of the genes within those regions. Chromosomal translocations : interchange of genetic parts from nonhomologous chromosomes.

10. Sources of damage There are two basic types of DNA damage. Endogenous : Substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates. Their provirus's remain in the genome and are passed on to the next generation.

11. Eg. (a) Reactive oxygen species  (ROS ) are chemically reactive molecules containing oxygen. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons.  ROS levels can increase dramatically. This may result in significant damage to cell structures. Cumulatively, this is known as oxidative stress.

12. (b) Oxidative deamination  is a form of deamination that generates oxoacids in the liver. The presence of nitrous acid can cause transition mutations, by converting cytosine to uracil. Primarily occurs in the liver and kidneys. (c)   Replication errors- DNA replication errors are caused by mispairings of a different nature of bases (e.g., bases with an extra proton, which can still bind but often with a mismatched nucleotide, such as an A with a G instead of a T).  

13. This type of mispairing is known as “wobble”. Replication errors can also involve insertions or deletions of nucleotide bases that occur during a process called strand slippage.

14. Exogenous damage caused by external agents RADIATION - Both ionizing and non-ionizing radiation can be harmful to organisms and can result in changes to the natural environments. Ultraviolet [UV 200-400 nm]  radiation from the sun. other radiation frequencies, including x-rays and gamma rays.

15. (b)HYDROLYSIS  is a chemical reaction during which molecules of water(H 2 O) are split into hydrogen cations (H + , conventionally referred to as protons) and hydroxide anions (OH − ) in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization.

16. (c)HUMAN MADE SOME MUTAGENE CHEMICAL Intercalating agents: These agents are planar ( flat) in structure and are approximately the same size as a purine-pyrimidine base pair.  In solution they can insert between stacked base-pairs.  The best known such agent is Ethidium bromide which is used to visualize DNA.

17.   VIRUS Many viruses have a replication strategy that involves double-stranded RNA (dsRNA). When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called dicer that cuts the RNA into smaller pieces.

18. Types of damage DNA undergoes several types of spontaneous modifications, and it also can react with many physical and chemical agents, some of which are endogenous products of normal cellular metabolism (eg.ROS)whereas others, including ionizing radiation and ultraviolet light, are threats from the external environment. Furthermore, the degree and spectrum of DNA damage depends on the sample source and the type of environment to which it was exposed.

19. There are five main types of damage to DNA due to endogenous cellular processes (1)Bases of oxidation DNA is also subject to attack from reactive oxygen species(eg-O 2 -,H 2 O 2 -).   For e.g..   8-oxo-7,8-dihydroguanine (8-oxoG).this are very highly mutagenic because it can base pair with adenine as well as with cytosine.

20. (2) Bases of Alkylating agents:   Certain alkylating agents, such as ethyl methane sulfonate (EMS) and ethyl ethane sulfonate (EES) add alkyl groups to purines, which can cause mispairing, and also destabilize the bond between the purine and deoxyribose, leaving apurinic sites. The absence of a base-pairing partner allows any base to be inserted during the next round of DNA synthesis. This frequently leads to transversions as well as transitions.

21. 3. Bases of Hydrolysis An Hydrolytic damage Spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process. This can occur in vitro through the use of bisulfite, which converts cytosine, but not5-methylcytosine. This is the most common single nucleotide mutation In DNA.

22. 4) Depurination - Depurination is an alteration of DNA in which the purine base (adenine or guanine) is removed from the deoxyribose sugar by hydrolysis of the beta-N-glycosidic link between them. After depurination, an apurinic site is formed where the sugar phosphate backbone remains and the sugar ring has a hydroxyl (-OH) group in the place of the purine.

23. 5) Mismatch of bases, due to errors in DNA replication, in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted.

24. Damage caused by exogenous agents comes in many forms. Some examples are 1.(a) UV-B light causes crosslinking between adjacent cytosine and thymine bases creating pyrimidine dimers. This is called direct DNA damage. It causes sunburn and it triggers the production of melanin.

25. (b). UV-A light creates mostly free radicals. The damage caused by free radicals is called indirect DNA damage. Indirect DNA damage occurs when a UV-photon is absorbed in the human skin by a chromophore that does not have the ability to convert the energy into harmless heat very quickly.

26. (2)Ionizing radiation such as that created by radioactive decay or in cosmic rays causes breaks in DNA strands. Low-level ionizing radiation may induce irreparable DNA damage leading to pre-mature aging and cancer.

27. (3)Thermal disruption at elevated temperature increases the rate of depurination (loss of purine bases from the DNA backbone) and single-strand breaks. For example, hydrolytic depurination is seen in the thermophilic bacteria, which grow in hot springs at 40-80 °C.   (4)Industrial chemicals such as vinyl chloride and hydrogen peroxide, and environmental chemicals such as polycyclic aromatic hydrocarbons found in smoke, soot and tar create a huge diversity of DNA adducts- ethenobases, oxidized bases.

28. Common Carcinogen In chemical agent carcinogen are more effective to DNA damage. A  carcinogen  is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit.

29. Function of carcinogen : After the carcinogen enters the body, the body makes an attempt to eliminate it through a process called biotransformation. The purpose of these reactions is to make the carcinogen more water-soluble so that it can be removed from the body. But these reactions can also convert a less toxic carcinogen into a more toxic carcinogen.

30. Some important carcinogen Aflatoxin B 1 : Aflatoxin B 1 , which is produced by the fungus  Aspergillus flavus growing on stored grains, nuts and peanut butter. By cigarettes - Tobacco smoke contains over 4000 chemical compounds, many of which are carcinogenic or otherwise toxic.

31. CONCLUSION- Organism can survive only if their DNA is replicated faithfully and is protected from chemical and physical damage that would change its coding properties. Mutagenesis and its repair are of concern to us because they permanently affect the genes that organisms inherit and sometimes causes major diseases like cancer.

32. REFERENCE Molecular biology of the cell - Albert's Molecular biology of the gene - J. D. Watson www.wikipedia.com Date-5/2/2014 Time-7 pm