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http://www.chem.udel.edu/chen-powerpoints. Download Chem 642 ppts from here. DNA STRUCTURE. DNA is composed of polynucleotide chains. The helical structure of DNA. Formation of Nucleotides. Structure of polynucleotide polymer. Each base has its preferred tautomeric form. - PowerPoint PPT PresentationTRANSCRIPT
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http://www.chem.udel.edu/chen-powerpoints
Download Chem 642 ppts from here
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DNA STRUCTUREDNA is composed of polynucleotide chains
The helical structure of DNA
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Formation of Nucleotides
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Structure of polynucleotide polymer
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Each base has its preferred tautomeric form
Purine and Pyrimidine
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Base tautomers; are frequent sources of errors during DNA synthesis
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The two strands of the double helix are held together by base pairing in an anti-parallel orientation
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The two chains of the double helix have complementary sequences
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What is a complementary sequence?
5’ATCGG, TGCAA, CCGCG, TAAGT 3’
(1) 5’ TAGCC, ACGTT, GGCGC, ATTCA 3’
(2) 5’ TGAAT, GCGCC, AACGT, GGCTA 3’
(3) 5’ ACTTA, CGCGG, TTGCA, CCGAT 3’
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Hydrogen bonding is important for specificity of base pairing
A:C incompatibility
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Base can flip out from the double helix
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DNA is usually a right-handed double helix
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Rotini
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The double helix has minor and major grooves
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If the DNA double helix looks the same no matter what sequences, how can a protein recognize a specific DNA sequence??
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The major groove is rich in chemical information
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A DNA recognition code.The edge of each base pair, seen here looking directly at the major or minor groove, contains a distinctive pattern of hydrogen bond donors, hydrogen bond acceptors, and methyl groups. From the major groove, each of the four base-pair configurations projects a unique pattern of features. From the minor groove, however, the patterns are similar for G–C and C–G as well as for A–T and T–A.
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The binding of a gene regulatory protein to the major groove of DNA.
Only a single contact is shown. Typically, the protein-DNA interface would consist of 10 to 20 such contacts, involving different amino acids, each contributing to the strength of the protein–DNA interaction.
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The double helix exists in multiple conformations
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CAMBRIDGE, Mass.-- Massachusetts Institute of Technology scientist Alexander Rich, best known for his discovery of left-handed DNA or Z-DNA and the three-dimensional structure of transfer RNA, is the recipient of the $250,000 Bower Award for Achievement in Science (2010).
Alexander Rich
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The propeller twist between the purine and pyrimidine base pairs
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DNA can sometimes form a left-handed helix (Z DNA)
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DNA strands can separate (denaturation) and reassociate (hybridization)
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Denaturation of DNA
When DNA is heated to 80+ degrees Celsius, its UV absorbance (260 nm) increases by 30-40%
This hyperchromic shift reflects the unwinding of the DNA double helix
Stacked base pairs in native DNA absorb less light
When Temperature is lowered, the absorbance drops, reflecting the re-establishment of stacking
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DNA denaturation curve
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If we use different DNA sequences to measure the Tm, do we get the same melting curves (same Tm)?
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• In duplex DNA, 10 bp per turn of helix • Circular DNA sometimes has more or less than
10 bp per turn - a supercoiled state • Enzymes called topoisomerases or gyrases can
introduce or remove supercoils • Negative supercoiling may promote DNA
denaturation
DNA TOPOLOGY
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Linking # is an invariant topological property of covalently closed, circular DNA (cccDNA); Linking # is composed of Twist & Writhe
L: Linking #; T: Twist #; W: Writhe # L=T+W; L can never be changed as long as no topoisomerase is used, and there is no nicks in DNA.
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Lk0 is the linking # of a fully relaxed cccDNA under physiological conditions
Relaxing DNA with Dnase I
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DNA in cells is negatively supercoiled
Superhelical density: s = DLK/Lko
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Nucleosomes introduce negative supercoiling in Eukaryotes
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Topoisomerases can relax supercoiled DNAChanging the linking # with topoisomerase II
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Topoisomerase II, makes a double-stranded break, allows anotherDouble-stranded DNA (from the same or other molecule) to passThrough. Requires ATP.
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Mechanism of topoisomerase I
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Prokaryotes have a special topo II (DNA Gyrase) that introduces supercoils into DNA; Topoisomerases also unknot and disentangle DNA molecules
If one circle carry a nick or gap
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Topoisomerases use a covalent protein-DNA linkage to cleave and rejoin strands
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Model for the reaction cycle catalyzed by Topo I
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DNA topoisomers can be separated by gel electrophoresis
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Ethidium ions cause DNA to unwind
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Nicholas Robert Cozzarelli, editor-in-chief of the journal Proceedings of the National Academy of Sciences and aprofessor of molecular and cell biology at the University of California, Berkeley.Courtesy of UC Berkeley.
Jim Wang shown here with his wife Sophia in Spain
Forty-one years ago, Jim Wang discovered the first of a family of enzymes crucial to the disentanglement of DNA strands or double helices during various cellular processes involving DNA, including replication, transcription, and repair. He coined the term “DNA topoisomerases” to describe the enzymes, and has been a leader in the field ever since. Now, the emeritus Mallinckrodt Professor of Biochemistry and Molecular Biology, who retired from MCB and Harvard in 2005, has written Untangling the Double Helix: DNA Entanglement and the Action of the DNA Topoisomerases (Cold Spring Harbor Laboratory Press, 2009)
‘‘If you want to be a leader inscience, you must be creative, think in anoriginal way. The good scientist knowsthe literature, whereas the really goodscientist knows when to forget the literature.’’[Howard Hughes Medical Institute(HHMI) ‘‘Ask a Scientist’’ featurein 2000 (www.hhmi.orgaskascientistmeet-scientistscientistscozzarelli.html;accessed March 20, 2006).]
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RNA STRUCTURE
Structural features of RNA
RNA contains Ribose and uracil and is usually single-stranded
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RNA chains fold back on themselves to form local regions of double helix similar to A-form DNA
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C(UUCG)G Tetraloop
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Pseudoknot
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Many non-W-C base pairs involved in the formation of RNA tertiary structures
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RNA can fold up into complex tertiary structures
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Some RNAs are enzymes (Ribozymes); Rnase P, RNA Self-splicingA hammerhead ribozyme cleaves RNA by the formation of a 2’, 3’ cyclic phosphate
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Did life evolve from an RNA world?
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Nobel Prize in Chemistry 1989 was awarded jointly to Sidney Altman and Thomas R. Cech "for their discovery of catalytic properties of RNA"
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PRESIDENT OBAMA MEETS U.S. LAUREATES OF 2010 KAVLI PRIZESJune 6th at the White House, President Barack Obama met in the Oval Office with the seven U.S. recipients of the 2010 Kavli Prizes to recognize and honor their seminal contributions to the three fields for which the Prizes are awarded - astrophysics, nanoscience and neuroscience.Joined by the President's science advisor, John P. Holdren, President Obama greeted Kavli Prize Laureates Roger Angel (University of Arizona), Jerry E. Nelson (University of California, Santa Cruz), Donald M. Eigler (IBM Almaden Research Center), James E. Rothman (Yale University), Richard H. Scheller (Genentech), Nadrian C. Seeman (New York University), and Thomas C. Südhof (Stanford University). Accompanying the laureates were Fred Kavli, Founder and Chairman of The Kavli Foundation; Robert W. Conn, President of The Kavli Foundation; and Wegger Chr. Strommen, the Norwegian Ambassador to the United States.
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