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Information Transfer in Cells. Information encoded in a DNA molecule is transcribed via synthesis of an RNA molecule The sequence of the RNA molecule is "read" and is translated into the sequence of amino acids in a protein. Review of DNA Structure. What is a nucleoside?
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Information Transfer in Cells • Information encoded in a DNA molecule is transcribed via synthesis of an RNA molecule • The sequence of the RNA molecule is "read" and is translated into the sequence of amino acids in a protein.
Review of DNA Structure • What is a nucleoside? • What is a nucleotide? • What forces hold DNA together as a helix? • Why are there two kinds of grooves in a B DNA helix? • What are the differences between A, B and Z forms of DNA
Sugar phosphate Nitrogenous base DNA (deoxyribonucleic acid) Building blocks = deoxyribonucleotides
Nitrogenous base Phosphate 5 HoCH2 oH HoCH2 oH o o 1 4 2 3 oH Links Nucleotide units H oH oH Ribose 5 1 4 2 3 Ribose - a pentose sugar - a furanose ring - in RNA - in nucleotides for energy metabolism (ATP) 2 deoxyribose - a pentose sugar - a furanose ring - in DNA
(11.2 Pentoses of Nucleotides) • D-ribose (in RNA) • 2-deoxy-D-ribose (in DNA) • The difference - 2'-OH vs 2'-H • This difference affects secondary structure and stability
11.1 Nitrogenous Bases • Pyrimidines • Cytosine (DNA, RNA) • Uracil (RNA) • Thymine (DNA) • Purines • Adenine (DNA, RNA) • Guanine (DNA, RNA)
Properties of Pyrimidines and Purines • Keto-enol tautomerism • Strong absorbance of UV light
Guanine Guanine
Nitrogenous base 5 HoCH2 oH NH2 o 1 4 N 2 3 oH 5 H o HoCH2 N o N-glycosidic linkage 1 4 2 3 oH H Nucleoside A purine/pyrimidine + deoxyribose or ribose Cytosine 4 5 3 ‘ 6 2 1 ‘ ‘ ‘ ‘ Cytidine
11.3 Nucleosides Linkage of a base to a sugar • Base is linked via a glycosidic bond • Named by adding -idine to the root name of a pyrimidine or -osine to the root name of a purine • Sugars make nucleosides more water-soluble than free bases
11.4 Nucleotides Nucleoside phosphates • Know the nomenclature • "Nucleotide phosphate" is redundant!
NH2 N O O O 5’ o O-P-O-P-O-P-OCH2 N - - - O O O O 1’ 4’ 2’ 3’ H OH - O O -P - 5’ OCH2 Nitrogenous base O 1’ 4’ 2’ 3’ H OH Deoxyribonucleic acid DNA is a nucleotide polymer linked by a 3’ to 5’ phosphodiester bond 5’ phosphate 3’ hydroxyl
Single-stranded DNA: Has polarity Has a hydrophilic side Has a hydrophobic side
5’ 5’ 3’ 3’ Double-stranded DNA 1) Pair of DNA chains in an antiparallel arrangement 2) Sugar-P backbone outside, aromatic rings (bases) inside 3) Bases pair specifically by H-bonding A pairs with T; G pairs with C [A] = [T] and [G] = [C] [purines] = [pyrimidines]
The “canonical” base pairs • The canonical A:T and G:C base pairs have nearly identical overall dimensions • A and T share two H-bonds • G and C share three H-bonds • G:C-rich regions of DNA are more stable • Polar atoms in the sugar-phosphate backbone also form H-bonds
Why a helix? Why not a ladder? • A side view of base pairs shows they are perpendicular to the helix axis • The heterocyclic bases have flat surfaces which are hydrophobic • To exclude water from between the rings, we should bring the bases closer together • One way to model them closer together is to “twist” the ladder into a helix
Right-handed twist ~10 base pairs per turn B form DNA helix
Summary: What holds DNA together? • Sugar-phosphate backbone outside • (1) minimizes electrostatic repulsion, • (2) interacts with water • Bases inside • (3) hydrogen-bonded • (4) plus base stacking by hydrophobic interactions
Major and minor grooves • The "tops" of the bases (as we draw them) line the "floor" of the major groove • The major groove is large enough to accommodate an alpha helix from a protein • Regulatory proteins (transcription factors) can recognize the pattern of bases and H-bonding possibilities in the major groove
Comparison of A, B, Z DNA • A: right-handed, short and broad, pitch is 2.3 A, 11 bp per turn • B: right-handed, longer, thinner, pitch is ~3.4 A, ~10 bp per turn • Z: left-handed, longest, thinnest, pitch is 3.8 A, 12 bp per turn
DNA Packaging • Human DNA total length is ~2 meters • Is packaged into a nucleus that is ~ 5 microns in diameter • This represents a compression of more than 100,000 fold • It is made possible by wrapping the DNA around protein spools called nucleosomes and then packing these into helical filaments
We reviewed: Chapter 11, Sections: 11.1, 11.2, 11.3, 11.4, 11.5 and the “DNA parts” of 11.6 Chapter 12, Sections: 12.2, 12.5