DNA Replication & Repair Lecture 2 2024-2025 PDF

Lecture 2 DNA Replication & Repair  Learning Objectives Understand the process of DNA replication Understand the molecular detail of DNA replication Appreciate the importance of DNA repair and mutations Basic Concept of DNA Replication Three models of DNA replication The exper...

Lecture 2 DNA Replication & Repair  Learning Objectives Understand the process of DNA replication Understand the molecular detail of DNA replication Appreciate the importance of DNA repair and mutations Basic Concept of DNA Replication Three models of DNA replication The experiment of Meselson and Stahl Click this link to watch an animation of the Meselson And Stahl Experiment Where in the cell cycle does replication occur? Origin of replication  4 stages of replication 1. Initiation 2. Unwinding 3. Primer synthesis 4. Elongation 1. Initiation and 2. Unwinding 3. RNA priming 4. Elongation Nucleotide  Synthesis of a new strand - Nucleotide incorporation Each nucleotide is a nucleotide TRIphosphate As each one joins, two phosphate groups are lost DNA pol add nucleotides Bacterial DNA Replication- leading strand Bacterial DNA replication – lagging strand Overview Origin of replication Leading strand Lagging strand Leading strand Lagging strand Single-strand Overall directions binding protein of replication Helicase Leading strand 5 3 DNA pol III 3 Primer Primase 5 Parental DNA 3 DNA pol III Lagging strand 5 4 DNA pol I DNA ligase 3 5 3 2 1 3 5 Click this link to watch an animation of DNA replication - https://youtu.be/s3nDTGg73AU DNA Repair  DNA replication not 100% accurate DNA Pol makes mistakes » Proof reading DNA repair mechanism – MMR https://www.youtube.com/watch?v=vP8-5Bhd2ag Hereditary DNA repair disorders Xeroderma pigmentosum: Mutations in the genes involved in NER Hypersensitivity to sunlight/UV Increased skin cancer incidence and premature aging Life expectancy of 29-37 years Werner's syndrome Premature aging Retarded growth Global incidence – 1:100,000 Normal growth until puberty Diagnosis ~24 Mutations Class of Human Disease(s) Linked Type of Mutation Description Mutation to This Mutation One base is incorrectly added during replication and replaces the pair in the Substitution Sickle-cell anemia corresponding position on the complementary strand One or more extra nucleotides are Point mutation Insertion inserted into replicating DNA, often One form of beta-thalassemia resulting in a frameshift One or more nucleotides is "skipped" Deletion during replication or otherwise excised, Cystic fibrosis often resulting in a frameshift One region of a chromosome is flipped Inversion Opitz-Kaveggia syndrome and reinserted A region of a chromosome is lost, Deletion resulting in the absence of all the genes Cri du chat syndrome in that area Chromosomal mutation A region of a chromosome is repeated, Duplication resulting in an increase in dosage from Some cancers the genes in that region A region from one chromosome is Translocation aberrantly attached to another One form of leukemia chromosome The number of tandem copies of Gene amplification Some breast cancers a locus is increased Copy number variation Expanding The normal number of repeated Fragile X syndrome, trinucleotide trinucleotide sequences is expanded Huntington's disease repeat  Types of point mutations Categorised in several way… – Based on the nature of the change e.g. point mutation. Base substitution Base insertion Base deletion Based on the consequence of the change – Missense – Frameshift Base-pair substitution  Base-pair insertion or deletion Click the link for an animation on mutation - https://www.youtube.com/watch?v=kp0esidDr-c Genetic polymorphism - the presence, in a population of two or more relatively common forms of a gene. Single nucleotide polymorphism (SNP) ABO - Blood group Cytochrome P450 Enzymes  Genome variation Polymorphi Mutation sm