Topic 3 Molecular Basis of Inheritance PDF

Topic 3: The Molecular Basis of Inheritance Watson and Crick Model of DNA, chromosome structure and function, DNA replication Learning objectives (LOBs) 1. Describe the structure and functions of DNA. 2. Describe the structure of chromosomes, including the structure and organisation of chromatin. 3....

Topic 3: The Molecular Basis of Inheritance Watson and Crick Model of DNA, chromosome structure and function, DNA replication Learning objectives (LOBs) 1. Describe the structure and functions of DNA. 2. Describe the structure of chromosomes, including the structure and organisation of chromatin. 3. Describe the process of DNA replication, including the processes of telomere replication and DNA repair. Reading: Campbell Biology, Chapter 16 1. DNA structure and function: The Search for the Genetic Material 20th century: The identification of the molecules of inheritance was as a major challenge to biologists Morgan’s group showed that genes are located on chromosomes => The 2 components of chromosomes—DNA and protein—became candidates for the genetic material Protein was a stronger candidate than DNA The Search for the Genetic Material The genetic material needed to have certain characteristics: – Contain information – Be easy to copy – Be variable to account for diversity between species The role of DNA in heredity was first discovered by studying bacteria and the viruses - simpler than plants, fruit flies, animals etc. Evidence That DNA is the genetic material Griffith experiment (1928):evidence that DNA can transform bacteria - Transformation: the genetic alteration of a cell due to uptake and incorporation of exogenous (foreign) DNA - He mixed 2 strains of the bacterium Streptococcus pneumoniae, a heat-inactivated pathogenic strain with living bacteria of a harmless (non-pathogenic) strain => some living cells became pathogenic -the transforming substance in Griffith’s experiment was later found to be DNA Hershey and Chase experiments (1952): studies of viruses that infect bacteria (bacteriophages) => evidence that viral DNA can program cells 1950: Erwin Chargaff reported that DNA composition varies between species => evidence of diversity Building a Structural Model of DNA Determination of how DNA structure accounts for its role in inheritance Maurice Wilkins and Rosalind Franklin (King’s College, London): used a technique called X-ray crystallography to study the molecular structure of DNA Watson and Crick (1953): produced the double-helical model for DNA structure - DNA was made up of 2 strands forming a double helix based on Franklin’s X-ray crystallographic images Fig. 16-6 (a) Rosalind Franklin (b) Franklin’s X-ray diffraction photograph of DNA James Watson and Francis Crick 1953: discovered the 3-dimensional structure of DNA Most of the experiments were performed by Rosalind Franklin who died before the awarding of the Nobel Prize for Physiology and Medicine in 1962. Watson and Crick never did any of the actual experiments James Watson (1928-) and Francis Crick (1916-2004) Watson and Crick published their work in 1953 Francis Crick (1916-2004) and James Watson (1928-) Building a Structural Model of DNA DNA structure: - 2 antiparallel sugar-phosphate backbones - the nitrogenous bases pairs are in the molecule’s interior Watson and Crick determined that adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C) The Watson-Crick model explains Chargaff’s rule Chargaff’s rule: in any species there is an equal number of A and T bases and an equal number of G and C bases Fig. 16-8 2 hydrogen bonds A=T G=C Purines Pyrimidines Adenine (A) Thymine (T) Guanine (G) Cytosine (C) 3 hydrogen bonds DNA is the genetic material DNA is the substance of inheritance Hereditary information is encoded in DNA and reproduced in all the cells of the body This DNA program directs the development of biochemical, anatomical, physiological, and (to some extent) behavioral traits The DNA Double Helix A DNA molecule has 2 polynucleotides spiraling around an imaginary axis, forming a double helix Figure 16.5 Sugar–phosphate backbone 5end The four bases in DNA Nitrogenous bases Thymine (T) Adenine (A) Cytosine (C) Phosphate Guanine (G) Sugar (deoxyribose) DNA nucleotide 3 end Nitrogenous base Fig. 16-7a 5end Hydrogen bond 3end 1 nm 3.4 nm 3end 0.34 nm (a) Key features of DNA structure (b) Partial chemical structure 5end DNA DOUBLE HELIX C G T A A T Nitrogenous bases G Sugar-phosphate backbone C G T A C C G Hydrogen bond T A Fig. 16-7b (c) Space-filling model The Structure of DNA DNA is made of monomers called nucleotides Each DNA nucleotide consists of: - a nitrogenous base - a pentose sugar (deoxyribose) - a phosphate group Nucleotide monomers Nucleotide = nitrogenous base + pentose sugar + phosphate group Nucleoside (Νitrogenous base +sugar) Nitrogenous base Phosphate group Sugar (pentose) Nucleotide Nucleoside = nitrogenous base + pentose sugar Nucleotide monomers In DNA, the sugar is deoxyribose Deoxyribose (in DNA) Fig. 5-27 5 end Nitrogenous bases Pyrimidines 5 C 3 C Nucleoside Nitrogenous base Cytosine (C) Thymine (T, in DNA) Uracil (U, in RNA) Purines Phosphate group 5 C Sugar (pentose) Adenine (A) Guanine (G) (b) Nucleotide 3 C Sugars 3 end (a) Polynucleotide, or nucleic acid Deoxyribose (in DNA) (c) Nucleoside components: sugars Ribose (in RNA) The DNA Double Helix Eukaryotic nuclear DNA molecules: – Consist of 2 polynucleotide strands that spiral around an imaginary axis forming a double helix – Antiparallel strands: each strand runs in an opposite direction to the other one => one runs 5’→3’ and the other in 3’→5’ direction – Sugar-phosphate backbone is on the outside – The nitrogenous bases form hydrogen bonds in a complementary fashion: A-T C-G – The 2 strands are complementary: if we know the sequence of one we can derive the sequence of the other 5' end 3' end Fig. 5-28 Sugar-phosphate backbones Base pair (joined by hydrogen bonding) Old strands Nucleotide about to be added to a new strand 3' end 5' end New strands 5' end 3' end 5' end 3' end 5’ 3’ Anti-parallel strands: run in opposite directions 3’ 5’ The 3’-5’ phosphodiester bond In DNA the nucleotides are connected phosphodiester bond to create a polymer Phosphodiester bond: between the 3’-OH group of the sugar molecule of one nucleotide and the 5’-phosphate group of the second nucleotide. During this condensation reaction a molecule of water is excluded. in a 3’-5’ DNA structure http://www.youtube.com/watch?v=qy8dk5iS1f0&feature=related 2. Chromosome structure Chromosomes: DNA packed with proteins Bacterial chromosome: - double-stranded circular DNA molecule associated with a small amount of protein - DNA is supercoiled in the nucleoid Eukaryotic chromosomes: double stranded linear DNA molecules associated with a large amount of proteins (histones) - located in the nucleus - consist of chromatin - Chromatin: DNA + histones (proteins) - The chromosomes are packed and supercoiled in different levels in order to fit into the nucleus Bacterial chromosome Circular double-stranded DNA molecule Only 1 chromosome DNA strands Loose form Eukaryotic chromosome DNA is packed together with proteins in chromosomes Fig. 16-21a Levels of chromatin packing in a eukaryotic chromosome Nucleosome (10 nm in diameter) DNA double helix (2 nm in diameter) H1 Histones DNA, the double helix (1) Histones Histone tail Nucleosomes, or “beads on a string” (10-nm fiber) (2) Chromosome structure: DNA packed with proteins Levels of chromatin packing in a eukaryotic chromosome Fig. 16-21b Chromatid (700 nm) 30-nm fiber Loops Scaffold 300-nm fiber Replicated chromosome (1,400 nm) 30-nm fiber (3) Looped domains (300-nm fiber) (4) Metaphase chromosome (5) Chromatin organisation DNA wrapped around nucleosomes as «beads on a string» 1Å = 10-10 m 1 nm= 10-9 m Looped domains (loops) Metaphase (replicated) chromosome: 2 chromatids Chromatin organisation Μetaphase chromosome Looped domains (300 nm) Chromatin fibers 30 nm Histones DNA wrapped around nucleosomes as «beads on a string» Double helix Metaphase chromosome: 2 chromatids Chromatid (700 nm) Nucleosome structure Each nucleosome consists of 8 histone molecules (Η2Α,H2B, H3,H4)2 + ds DNA (168 base pairs) H1 histone: -Located between the nucleosomes -Role: stabilizes the interaction between DNA and nucleosomal histones Nucleosome structure: histone octamer 10 nm Histone octamer Chromatin structure and organisation Euchromatin: Loosely packed chromatin (active form)  Enables replication and transcription  enables gene expression Heterochromatin: highly condensed chromatin (inactive form)  inhibits replication and transcription  inhibits gene expression Chromatin structure and organisation Chromatin undergoes changes in packing during the cell cycle: During interphase: Most chromatin is loosely packed (euchromatin) => enables gene expression - Chromosomes are not condensed: some chromatin is organized into a 10-nm fiber but most is compacted into a 30nm fiber During mitosis: chromatin is highly condensed into heterochromatin => inhibition of gene expression Exception: centromeres and telomeres which are always highly condensed into heterochromatin Histone modification and chromatin structure Histones can undergo chemical modifications (e.g. methylation, acetylation) that result in changes in chromatin organization => changes in gene expression Histone modification can result in changes in gene expression: e.g. gene silencing (inhibition of gene expression) => Involved in many diseases (e.g. cancer) Epigenetics: the study of cellular/physiological traits that are NOT caused by changes in the DNA sequence (caused by changes in gene expression) - e.g. DNA methylation, histone modification Histone modification and chromatin structure Histone acetylation: - converts heterochromatin into euchromatin - loss of the histone (+) charge due to acetylation weakens their interaction with DNA  Converts chromatin into its loose active form (euchromatin)  Enables gene expression Histone deacetylation: - Inactivates chromatin –converts it into heterochromatin - Restores (+) charge of histone => strengthens their interaction with DNA Histone modification and chromatin structure Co-activator Co-repressor activator repressor Acetylated histones Active chromatin (euchromatin) Deacetylated histones Inactive chromatin (heretochromatin) HAT = histone acetyl-transferases HDAC = histone deacetylases https://www.youtube.com/watch?v=eYrQ0EhVCYA Localization of euchromatin and heterochromatin in nucleus 3. DNA replication and repair The 2 strands of DNA are complementary => each strand acts as a template for building a new strand in replication Semiconservative model of replication: when a double helix replicates each daughter molecule will have 1 old strand (derived or “conserved” from the parent molecule) and 1 newly synthesized strand The parent molecule unwinds and 2 new daughter strands are built based on base-pairing rules DNA replication is fast and highly accurate More than a dozen enzymes and other proteins participate in DNA replication and repair Fig. 16-9-3 DNA replication Semiconservative model: when a double helix replicates, each daughter molecule will have 1 old strand (derived or “conserved” from the parent molecule) and 1 newly made strand New strand Parental strand A T A T A T A T C G C G C G C G T A T A T A T A A T A T A T A T G C G C G C G C (a) Parent molecule (b) Separation of strands (c) “Daughter” DNA molecules, each consisting of one parental strand and one new strand DNA replication: Origins of Replication Replication begins at special sites called origins of replication The DNA strands are separated opening up a replication “bubble” A eukaryotic chromosome may have hundreds or even thousands of origins of replication Bidirectional replication: Replication proceeds in both directions from each origin until the entire molecule is copied Animation: Origins of Replication DNA replication Fig. 16-12a Prokaryotic Origins of Replication Origin of replication Parental (template) strand Daughter (new) strand Doublestranded DNA molecule Replication fork Replication bubble 0.5 µm Two daughter DNA molecules (a) Origins of replication in E. coli E. Coli chromosome: circular, has only 1 origin of replication. Replication is bidirectional. Fig. 16-12b Eukaryotic Origins of Replication Origin of replication Double-stranded DNA molecule Parental (template) strand Daughter (new) strand 0.25 µm Bubble Replication fork Two daughter DNA molecules (b) Origins of replication in eukaryotes Eykaryotic chromosomes: have several replication origins. Replication is bidirectional. Initiation of Replication Replication fork: a Y-shaped region at the end of each replication bubble where new DNA strands are elongating Helicases: enzymes that untwist the double helix at the replication forks Single-strand binding protein: binds and stabilizes single-stranded DNA until it can be used as a template Topoisomerase: corrects “overwinding” ahead of replication forks by breaking, swiveling, and rejoining DNA strands Initiation of Replication DNA polymerases’ limitations: They can only add nucleotides to a pre-existing nucleotide chain => cannot initiate synthesis of a polynucleotide chain from scratch without a pre-existing nucleotide chain They can only add nucleotides in the 5’-3’ direction (i.e. to the 3’ end of a nucleotide) Primase: - Enzyme that synthesizes a short RNA primer (5–10 nucleotides long) from scratch using the parental DNA as a template - The free 3’ end of the RNA primer serves as the starting point for synthesis of the new DNA strand by DNA polymerase Initiation of Replication Primase Single-strand binding proteins 3 Topoisomerase 5 3 Replication fork Helicase 5 5 RNA primer 3 Elongation: Synthesizing a New DNA Strand DNA polymerases: - enzymes that catalyze the elongation of new DNA at a replication fork - require a primer and a DNA template strand Elongation rate: 500 nucleotides/sec in bacteria, 50 nucleotides/sec in human cells Elongation of New DNA Strand Each nucleotide that is added to a growing DNA strand comes from a nucleoside triphosphate (NTP) Nucleoside analogues Modified 3’-OH group AZT (azido-deoxy-thymidine): blocks replication due to modified 3’OH group (anti-retroviral drug) Synthesizing a New DNA Strand New strand 5’ end Sugar A Base Phosphate Template strand 3’ end 3’ end T A T C G C G G C G C T A 3’ end DNA polymerase A Pyrophosphate C Nucleoside triphosphate Fig. 16-14 5’ end 5’ end 3’ end C 5’ end Elongation: Synthesizing a New DNA Strand Example: dATP supplies adenine (A) to DNA - dATP= deoxy-adenosine triphosphate - ATP= adenosine triphosphate (ribonucleotide) - dATP is similar to ATP, the difference is in their sugars: dATP has deoxyribose while ATP has ribose -As each monomer of dATP joins the DNA strand, it loses 2 phosphate groups as a molecule of pyrophosphate dATP structure vs ATP structure deoxyribose Deoxyadenosine triphosphate (dATP) ribose Antiparallel Elongation DNA polymerases add nucleotides only in 5’-3’ direction  Therefore, a new DNA strand can elongate only in the 5’-3’ direction  They can never add a nucleotide to the 5’ end Replication fork Leading strand synthesis DNA polymerase III copies the 3’- 5’ strand => synthesizes a leading strand continuously in 5’→ 3’ direction => 2 leading strands per bubble are made Overview Origin of replication Leading strand Lagging strand 5 3 3 Primer 3 5 3 5 3 5 3 5 Leading strand Lagging strand Overall directions of replication 5 DNA replication: Leading strand synthesis Origin of replication Fig. 16-15b 3 5 RNA primer 5 “Sliding clamp” 3 5 Parental DNA DNA pol III 5 5 3 5 3 Lagging strand synthesis To copy the 5’-3’ strand, DNA polymerase III must work in the direction away from the replication fork ( in 5’→3’ direction) => The lagging strand is synthesized discontinuously as segments called Okazaki fragments which are later joined together by DNA ligase Overview Origin of replication Leading strand Lagging strand Lagging strand 2 1 Leading strand Overall directions of replication Lagging strand synthesis 1. Primase: synthesizes short RNA primers 2. DNA polymerase III: synthesizes Okazaki fragments by adding DNA nucleotides to each primer in the 5’→3’ direction (moving away from replication fork) 3. DNA polymerase I: degrades the RNA primers and replaces with DNA nucleotides 4. DNA ligase joins DNA fragments to the subsequent Okazaki fragments Fig. 16-16b6 Primase 3 DNA REPLICATION: LAGGING STRAND SYNTHESIS 5 Template strand Primase joins RNA nucleotides into a primer. 5 3 DNA Pol III adds DNA nucleotides to the primer, forming Okazaki fragment 1. DNA pol III 3 RNA primer 5 1 After reaching the next RNA primer to the right, DNA pol III detaches. 1 5 3 5 3 5 DNA pol III 2 1 5 3 5 DNA pol I 2 3 3 5 Okazaki fragment 3 3 5 3 1 5 DNA ligase 1 2 Overall direction of replication 3 5 After fragment 2 is primed, DNA pol III adds DNA nucleotides until it reaches the fragment 1 primer and detaches DNA pol I replaces the RNA primer with DNA, adding to the 3’end of fragment 2 DNA ligase forms a bond between the newest DNA and the DNA of fragment 1. Table 16-1 Fig. 16-17 Overview of bacterial DNA replication Overview Origin of replication Lagging strand Leading strand Leading strand Lagging strand Overall directions of replication Single-strand binding protein Helicase 5 Leading strand 3 DNA pol III 3 Parental DNA Primer 5 Primase 3 Primer 5 DNA pol III 4 Lagging strand DNA pol I 3 5 Primer 3 2 DNA ligase 1 3 5 Figure 16.UN03 Summary of bacterial DNA replication DNA pol III synthesizes leading strand continuously Parental DNA 3 5 DNA pol III starts DNA synthesis at 3 end of primer, continues in 5→ 3 direction 5 3 5 Helicase Origin of replication Lagging strand synthesized in short Okazaki fragments, later joined by DNA ligase 3 5 Primase synthesizes a short RNA primer DNA pol I replaces the RNA primer with DNA nucleotides Figure 16.16a Overview of DNA replication Leading strand Origin of replication Lagging strand Lagging strand 2 1 Overall directions of replication Leading strand Figure 16.18 DNA pol III Parental DNA 5 3 5 3 3 5 5 Connecting protein 3 Helicase 3 DNA pol III 5 Leading strand 3 5 Lagging strand Lagging strand template DNA replication http://highered.mheducation.com/olc/dl/120076/bio23.swf http://www.youtube.com/watch?v=hfZ8o9D1tus http://www.youtube.com/watch?v=gW3qZF9cLIA Replicating the Ends of DNA Molecules Limitations of DNA polymerase create problems for the linear DNA of eukaryotic chromosomes The replication machinery does not provide a way to complete the 5’ ends => Repeated rounds of replication produce shorter DNA molecules This is a problem only for eukaryotic cells that have linear chromosomes and not for prokaryotic cells that have circular chromosomes Replicating the Ends of DNA Molecules Τelomeres: - The ends of eukaryotic chromosomes - They consist of the repetitive sequence (TTAGGG)n bound to several proteins Role of telomeres: They protect the chromosomal ends from erosion, degradation, and recombination with other chromosomes => telomeres postpone (but do not prevent) the shortening of DNA molecules => postpone the erosion of genes near the ends of DNA molecules It has been proposed that the shortening of telomeres is connected to aging Mouse chromosomes with telomeres (stained orange) 1 µm Fig. 16-20 Τelomeres : the end- replication problem The end-replication problem (telomere replication problem): - There is no Οkazaki fragment for the replication of the 3΄ end of the chromosomes => Generation of 3’ projections at the two 3’ ends In every DNA replication round (S-phase), a small region of the telomere cannot be replicated => In each cell division some base pairs are lost (50-200 bp) Fig. 16-19 5 Leading strand Lagging strand Ends of parental DNA strands 3 Last fragment Previous fragment RNA primer Okazaki fragment Lagging strand 5 3 Parental strand DNA part lost on lagging strand due to the absence of Okazaki fragment at 5’ end Removal of primers by DNA pol I and replacement with DNA only where a 3 end is available (DNA pol I cannot add nucleotides from scratch) Parental strand 3 Second round of replication 3’-projection Chromosome part lost in next replication round Lagging strand 5 5 3 New leading strand 5 New lagging strand 3 Further rounds of replication Shorter and shorter daughter molecules Telomerase Τelomerase: enzyme that conserves the telomere length The replication capacity of the cells is depended on the length of the telomeres Role of telomere shortening: protects cells from carcinogenesis by limiting the number of cell divisions (Hayflick’s limit) Shortening of the telomeres (< 4-7kb) due to the incomplete replication the chromosome ends leads to replicative senescence (aging) Senescence: permanent cell cycle arrest after a cell has reached a certain number of cell divisions (Hayflick’s limit) Telomerase Ribonucleic enzyme that prevents the shortening of telomeres (telomere size should be 15-20 kb) Synthesizes the repetitive sequence (ΤΤΑGGG) of the telomeres using a template RNA primer plus the enzyme reverse transcriptase Telomerase consists of: - hTERT (reverse transcriptase) - Template RNA primer Human somatic cells: absence of active telomerase (hTERT) Activated telomerase only in: - Germ cells, stem cells, hair follicle cells (epithelial cell type), activated lymphocytes and several types of cancer cells Telomerase Regulation of telomerase activity: -Active in germ cells: if chromosomes of germ cells became shorter in every cell cycle => essential genes would eventually be missing from the gametes they produce -Inactive in most types of somatic cells: except stem cells, hair follicle cells, activated lymphocytes -Abnormally active in some cancer cells => may allow cancer cells to persist (continuously proliferate) Telomerase Telomere end Newly synthesized DNA Reverse transcriptase RNA template https://www.youtube.com/watch?v=2NS0jBPurWQ Proofreading and Repairing DNA Replication errors can occur during DNA replication such as errors in base pairing  Proofreading: corrects errors during DNA replication. -DNA polymerases proofread newly made DNA replacing any incorrect (mispaired) nucleotides -DNA polymerases have 3'→5' exonuclease activity that mediates proofreading during replication => removal of mismatched bases and replacement with correct ones Other types of DNA damage (exogenous/environmental): - Chemicals: e.g. certain molecules in cigarette smoke (benzo-α-pyrene) - Radiation: UV light, X-rays, radioactivity Proofreading DNA repair mechanisms DNA repair mechanisms (for single strand breaks): 1. Mismatch repair (MMR): repair enzymes correct any remaining errors in base pairing (mismatched bases) that commonly occur during DNA replication (replication errors). MMR occurs immediately after DNA replication (as most replication errors are detected and repaired by proofreading during replication). 2. Base excision repair (BER): removes damaged bases (small non-helix distorting base lesions) 3. Nucleotide excision repair (NER): removes bulky (helixdistorting) DNA lesions (e.g. thymine dimers caused by UV light) - a nuclease cuts out and replaces damaged stretches of DNA Mismatch repair (MMR) Base excision repair (BER) Nucleotide excision repair (NER) Nuclease DNA polymerase DNA ligase Fig. 16-18 Inherited DNA repair disorders Example: Xeroderma pigmentosum => impaired NER (in Xeroderma pigmentosum) Xeroderma pigmentosum Autosomal recessive genetic disorder Caused by a mutation in the genes encoding for the NER repair enzymes responsible for repairing UV lightinduced DNA damage Ultraviolet light (UV) causes the production of thymine dimers (Τ-Τ) in DNA The nucleotide excision repair (NER) DNA repair mechanism is normally able to repair this damage In Xeroderma pigmentosum patients, this DNA repair mechanism is inactive => They are highly susceptible to skin cancers (e.g.melanoma) Xeroderma pigmentosum DNA damage and repair DNA Damage type Mismatched bases Source Repair Mechanism Replication errors (mismatched bases) Mismatch repair (MMR) Chemical modification of bases Chemicals that can damage Base Excision Repair Colorectal and DNA bases (e.g. alkylating (BER) gastric cancers agents, oxidative DNA damage, free radicals) Bulky DNA adducts Pyrimidine (thymine) dimers (UVB light), intercalating chemicals (benzo[a]pyrene; distort the double helix) Double-strand Ionizing radiation breaks (radioactivity, X-rays, γrays) Inherited DNA repair disorders Hereditary Nonpolyposis Colon Cancer (HNPCC) Nucleotide excision repair (NER) Xeroderma Pigmentosum Homologous recombination (HR) and Non-homologous end joining (NHEJ) BRCA1 and BRCA2 defects (predisposition to breast cancer), chromosomal translocations 1 Evolutionary Significance of Altered DNA Nucleotides Error rate after proofreading repair is low but not zero DNA damage may be recognized and repaired. Failure to repair the damage results in a mutation which cannot be repaired Mutations: nucleotide sequence changes => may become permanent and can be passed on to the next generation Mutations are the source of the genetic variation upon which natural selection operates Mutations Changes in the sequence of the DNA bases (nucleotides) Source of new alleles: – Some are harmful (e.g. carcinogenic) – Some are beneficial => usually favoured by natural selection – Some are neither harmful nor beneficial Environmental Mutagens: cause DNA damage Summary - - DNA structure (e.g. nucleotide structure, base pairing, double helix) Chromosome structure: Eukaryotes: linear double stranded DNA, chromatin = DNA + histones, euchromatin/heterochromatin, levels of chromatin organisation, nucleosomes, histone modifications Prokaryotes: circular double stranded DNA DNA replication: Replication process Telomere replication Repair and proofreading mechanisms SBA example DNA repair is: A. Only important during replication. B. Found in some species. C. Vital to maintaining DNA’s integrity. D. An inherited disorder. Animations http://www.youtube.com/watch?v=2m5j5pymtQQ& feature=related Animations http://www.youtube.com/watch?v=sf0YXnAFBs8&feature=related