DNA Oxidation Society For Free Radical Biology and MedicineSchafer 1 DNA Oxidation: A Simple Overview Freya Q. Schafer, Ph.D. Free Radical and Radiation.

Slides:

Advertisements

Similar presentations

THE NUCLEIC ACIDS.

Advertisements

DNA Repair. -Errors (at a rate of 1x10 -9 ) are introduced during DNA replication -DNA in cells is constantly being altered by cellular constituents,

Pentose Phosphate Pathway Generation of NADPH and Pentoses COURSE TITLE: BIOCHEMISTRY 2 COURSE CODE: BCHT 202 PLACEMENT/YEAR/LEVEL: 2nd Year/Level 4, 2nd.

THE NUCLEIC ACIDS © 2007 Paul Billiet ODWSODWS. Friedrich Miescher in 1869 isolated what he called nuclein from the nuclei of pus cells Nuclein was shown.

Chapter 8.3: Nucleic Acid Chemistry CHEM 7784 Biochemistry Professor Bensley.

Nucleic Acids & Protein Synthesis Chapter Structure of DNA Phosphate group Nitrogen-containing base Sugar (deoxyribose)

AP Biology Nucleic acids AP Biology Nucleic Acids.

DNA damage, repair and recombination

Figure Distinguishing Characteristics of DNA and RNA

Oxidants and Aging Rolf J. Mehlhorn Lawrence Berkeley Laboratory

DNA Repair. Cell Cycle Checkpoint activation DNA Repair: Base Excision Repair Nucleotide excision repair Mismatch repair DSB repair SENESCENCE / APOPTOSIS.

7 Mechanisms of Mutation and DNA Repair. Mutations Spontaneous mutation : occurs in absence of mutagenic agent Rate of mutation: probability of change.

Ascorbate (Vitamin C), its Antioxidant Chemistry

Redox State Society For Free Radical Biology and MedicineSchafer & Buettner 1 Redox State and Redox Environment Freya Q. Schafer and Garry R. Buettner.

Mutations, Mutagenesis, and Repair Chapter 10. The Problem DNA extremely long, fragile DNA extremely long, fragile Subject to both physical and chemical.

DNA Damage. DNA damage DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 1,000 to 1,000,000.

Action spectrum (approximate) for the induction of erythema in human skin, and average intensity at the earth’s surface. The figure also.

Review of Biological Chemistry. Biologically Important Elements.

Mutations and mutagens

Nucleic Acids The blueprints. Types of Molecules Polymers of nucleotides DNA: code for genetic information RNA –mRNA intermediates in protein synthesis.

2.6: Structure of DNA and RNA

Chapter 18 – Gene Mutations and DNA Repair

D.N.A. DeoxyriboNucleic Acid

Recall the structure of DNA Describe the differences of DNA Explain how DNA is utilised for different purposes.

Chapter 14 Molecular Mechanisms of Mutation and DNA Repair Jones and Bartlett Publishers © 2005.

How Genes Work. Structure of DNA DNA is composed of subunits – nucleotides Three parts Deoxyribose (5-carbon sugar) Phosphate group Nitrogen base – 2.

Regents Biology Nucleic Acids Information storage.

1.Chemistry of reactive oxygen species (ROS) 2. Sources, defense mechanisms and pathological consequences 3. A survey of pathological conditions connected.

Gihan E-H Gawish, MSc, PhD Ass. Professor Molecular Genetics and Clinical Biochemistry KSU 10 TH WEEK DNA damage, repair & Mutagenesis.

Antioxidants for Health and Sports

DNA RNA  Made up of C, H, O, N, P Nucleotides are the monomers of Nucleic Acids Phosphate Group 2.5-Carbon Sugar (Dexoyribose or Ribose)

Biochemistry Unit.  Nucleic acids direct the growth and development of every living organism. Included in this group is DNA, RNA, and ATP. As well, the.

AS Biology. Gnetic control of protein structure and function.

Biology Ch. 11 DNA and Genes DNA  DNA controls the production of proteins Living tissue is made up of protein, so DNA determines an organism’s.

AP Biology Nucleic Acids Information storage proteins DNA Nucleic Acids  Function:  genetic material  stores information  genes  blueprint for building.

DNA Introduction. What is DNA? Genetic information of life Type of Nucleic Acid Double Stranded.

Nucleic Acids. Nucleic acids are large biomolecules (polymers) – essential for all known forms of life Include DNA and RNA Made from long strands of nucleotides.

2015/04/10 Jun Min Jung MOLECULAR BIOLOGY & BIOCHEMISTRY.

DNA and RNA. Rosalind Franklin Worked with x-ray crystallography Discovered: That DNA had a helical structure with two strands.

Page 47.  Chemical Composition  Carbon, hydrogen, oxygen, nitrogen and phosphorus  Monomer  Nucleotide Sugar Phosphate Nitrogen base.

Chemical and Physical properties of nucleic acid

DNA does what ? Gives instructions to the cells.

Reactive Oxygen Species in Foods

THE NUCLEIC ACIDS © 2007 Paul Billiet ODWS.

Nucleic Acids. Nucleic Acids Made from long strands of nucleotides (monomers) Nucleic acids are large biomolecules (polymers) – essential for all known.

DNA The Molecule of Life.

DNA damage, repair & Mutagenesis

Nucleic Acids Information storage

DNA? ... RNA? ... What's the difference?

Ribonucleic Acid -RNA = ribonucleic acid

Notes: RNA Transcription.

The Structure & Function of DNA, RNA, and protein.

DNA & Protein Synthesis

THE NUCLEIC ACIDS © 2016 Paul Billiet ODWS.

DNA & RNA Notes Unit 3.

THE NUCLEIC ACIDS Nucleic acids are the third class of biopolymers (polysaccharides and proteins being the others) © 2016 Paul Billiet ODWS.

Nucleosides & Nucleotides

THE NUCLEIC ACIDS © 2007 Paul Billiet ODWS.

Production of reactive oxygen species.

Lesson 8 Nucleic Acids.

Biological Compounds You are what you eat.

Structure and function of DNA

Proteins and Nucleic Acids

Proteins and Nucleic Acids

Richard A.F. Clark Journal of Investigative Dermatology

THE NUCLEIC ACIDS © 2016 Paul Billiet ODWSODWS. Friedrich Miescher in 1869 Isolated what he called nuclein from the nuclei of pus cells Nuclein was shown.

Presentation transcript:

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 1 DNA Oxidation: A Simple Overview Freya Q. Schafer, Ph.D. Free Radical and Radiation Biology Program Department of Radiation Oncology The University of Iowa Iowa City, IA Tel: The Virtual Free Radical School

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 2 Components of DNA and RNA bases sugars DNA-Structure adapted from: National Human Genome Research Institute (NHGRI); by artist Darryl Leja phosphate back bone

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 3 Hot Spots for Free Radical Attack

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 4 Oxidative Damage to the Bases Adapted from: von Sonntag C. (1987) The Chemical Basis of Radiation Biology. Taylor & Francis London, NY. HO attack on pyrimidines

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 5 Oxidative Damage to the Bases Adapted from: von Sonntag C. (1987) The Chemical Basis of Radiation Biology. Taylor & Francis London, NY. HO attack on purines

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 6 Examples of Oxidized DNA Bases Adapted from: Dizdaroglu M. (1992) Free Radic Biol Med. 10: Dizdaroglu M. (2002) Free Radic Biol Med. 32:

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 7 Oxidation of DNA can lead to Mutations Misreading of 8- OHdGua can lead mutation (GC  AT transversion).

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 8 Oxidation of 5-methylcytosine leads to Rapid Deamination. Adapted from: Zuo S, Boorstein RJ, Teebor GW. (1995) Oxidative damage to 5-methylcytosine in DNA. Nucl Acids Res. 23: Deamination can result in: a) loss of methylation, b) mutation (GC  AT transition).

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 9 Oxidant Attack on Sugar The 4’-hydrogen is the weak point Adapted from: C. von Sonntag (1987) The Chemical Basis of Radiation Biology. Taylor & Francis London, NY.

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 10 Transfer of Damage from a Base to a Sugar Adapted from: C. von Sonntag (1987) The Chemical Basis of Radiation Biology. Taylor & Francis London, NY. Example: Uracil radical reacting with ribose

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 11 DNA Strand Breaks DNA single strand breaks result because of the collapse of the sugar. They are the most common damage inflicted by ROS.

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 12 Damage by RNS NO + O 2 -  ONOO - + H +  ONOOH  “ NO 2 + HO “ Peroxynitrite is a strong oxidant formed by reaction of nitric oxide with superoxide: Spencer PE. et al. (1996) Chem Res Toxicol. 9:

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 13 Reaction of Peroxynitrite with 2’-Deoxyguanosine Continued Adapted from Douki T. et al. (1996) Chem Res Toxicol. 9:3-7.

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 14 DNA Damage by UV light Absorption spectra of DNA (calf thymus) and a protein (BSA) at equal conc. (  20  g/mL). Adapted from: Harm W. (1980) Biological Effects of Ultraviolet Radiation. Cambridge University Press. Adapted from: Halliwell B, Gutteridge JM. (1989) Free Radicals in Biology and Medicine Clarendon Press Oxford 2 nd Ed.

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 15 Photosensitization can Produce Singlet Oxygen or Hydroxyl Radical

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 16 DNA-Protein-Crosslinking (DPC): Produced by UV Light or HO Attack Action spectrum for the relative induction of DNA- protein crosslinks by UV and visible radiations Peak GJ, Peak M J, Sikorski RS, Jones CA. (1985) Photochem Photobiol. 41:

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 17 1 O 2 can React with DNA Bases 1 O 2 reacts with dG to form 8 OHdG Adapted from: Devasagayam TPA, Steenken S, Obendorf MSW, Schulz WA, Sies H. (1991) Biochemistry. 30:

DNA Oxidation Society For Free Radical Biology and MedicineSchafer 18 Summary Oxidants can react with the DNA bases or sugars Guanine is the most sensitive base towards oxidative attack. More then 20 different oxidized base products are known; some can be mutagenic. Damage to the sugar can result in strand breaks. Electron rich moieties are the preferred sites of attack.