* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download DNA structure and replication Three key features needed for any
DNA barcoding wikipedia , lookup
Frameshift mutation wikipedia , lookup
Human genome wikipedia , lookup
Zinc finger nuclease wikipedia , lookup
Designer baby wikipedia , lookup
DNA sequencing wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Mitochondrial DNA wikipedia , lookup
Comparative genomic hybridization wikipedia , lookup
Holliday junction wikipedia , lookup
DNA profiling wikipedia , lookup
Genomic library wikipedia , lookup
Cancer epigenetics wikipedia , lookup
No-SCAR (Scarless Cas9 Assisted Recombineering) Genome Editing wikipedia , lookup
SNP genotyping wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Bisulfite sequencing wikipedia , lookup
Microevolution wikipedia , lookup
DNA damage theory of aging wikipedia , lookup
DNA vaccination wikipedia , lookup
Primary transcript wikipedia , lookup
United Kingdom National DNA Database wikipedia , lookup
Genealogical DNA test wikipedia , lookup
Gel electrophoresis of nucleic acids wikipedia , lookup
Non-coding DNA wikipedia , lookup
Microsatellite wikipedia , lookup
Cell-free fetal DNA wikipedia , lookup
Molecular cloning wikipedia , lookup
History of genetic engineering wikipedia , lookup
Epigenomics wikipedia , lookup
DNA replication wikipedia , lookup
DNA nanotechnology wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
DNA polymerase wikipedia , lookup
Point mutation wikipedia , lookup
Extrachromosomal DNA wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
DNA supercoil wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Nucleic acid double helix wikipedia , lookup
Nucleic acid analogue wikipedia , lookup
Helitron (biology) wikipedia , lookup
DNA structure and replication What was known? 1) Hereditary factors were associated with specific traits 2) One-gene-one-protein model - from mapping genes for biosynthetic pathways 3) Genes are on chromosomes 4) Chromosomes are made up of DNA and protein Three key features needed for any model of DNA structure 1) Must allow for faithful replication 2) Must have information content 3) Must be able to change in order to explain mutations 1 Rosalind Franklin James Watson Maurice Wilkins Francis Crick Linus Pauling X-ray diffraction Photograph of B-DNA Nature 171, 737-738 (1953) © Macmillan Publishers Ltd. Molecular structure of Nucleic Acids WATSON, J. D. & CRICK, F. H. C. Features of the double helix A Structure for Deoxyribose Nucleic Acid 1) Two parallel strands We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest………… 2) Bases held together by H-bonds 3) Phosphodiester backbone 4) The base is attached to the position 1 on the sugar 5) Base pair stack - provides Figure 1. This figure is purely diagrammatic. The two ribbons symbolize the two phophate-sugar chains, and the horizonal rods the pairs of bases holding the chains together. The vertical line marks the fibre axis. …………….It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material. stability 6) Contains a major and minor groove Three key features needed for any model of DNA structure 1) Must allow for faithful replication - each strand of DNA serves as a template for replication 2) Must have information content - the sequence of bases predict the sequence of amino acids in proteins 3) Must be able to change in order to explain mutations changes in DNA sequences result in changes in the amino acid sequence in proteins 2 Proposed models for DNA replication Hallmarks of DNA synthesis 1) Accuracy (less than 1 mutation in 10,000 bases copied 2) Speed (1000bases/sec) 3 Players: DNA gyrase - a topoisomerase Primase - RNA polymerase - synthesizes a primer Helicase - unwinding enzyme - acts upstream of the replication fork Okazaki fragments - DNA fragment synthesized on lagging strand SS binding proteins - bind single stranded DNA around the replication fork DNA ligase - links the okazaki fragments by making a phosphodiester bond DNA polymerase - synthesizes the new DNA strands Sliding clamp - DNA binding protein - keeps the DNA polymerase bound to DNA The replisome A comparison of primer-template DNA bound to four DNA polymerases Steitz, T. A. J. Biol. Chem. 1999;274:17395-17398 4 Chromatin assembly on eukaryotic chromosomes CAF-1: chromatin assembly factor 1: binds histones and targets them to the replication fork PCNA: proliferating cell nuclear antigen - the eukaryotic version of the clamp protein 5 How do you replicate the ends of linear chromosomes without losing DNA sequence? The problem: Telomerase is a non-template dependent DNA polymerase 6 Replication of chromosome ends by telomerase (a reverse transcriptase) 5’-TTGGGGTTGGGGTTGGGG-3’ 3’-AACCCCAACCCC-5’ Telomerase extends 3’ end (non-template synthesis) 5’-TTGGGGTTGGGGTTGGGGTTGGGGTTGGGG-3’ 3’-AACCCCAACCCC-5’ Extension of incomplete strand by DNA polymerase (template dependent) 5’-TTGGGGTTGGGGTTGGGGTTGGGGTTGGGG-3’ 3’-AACCCCAACCCCAACCCCAACCCC-5’ 7