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

DNA (deoxyribonucleic acid) Building blocks = deoxyribonucleotides Sugar Nitrogenous base phosphate

Ribose oHoH oHoH oHoH H o CH 2 o Ribose - a pentose sugar - a furanose ring - in RNA - in nucleotides for energy metabolism (ATP) H oHoH oHoH H o CH 2 o deoxyribose - a pentose sugar - a furanose ring - in DNA Nitrogenous base Phosphate Links Nucleotide units

(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)

Naturally occurring purine derivatives

Properties of Pyrimidines and Purines Keto-enol tautomerism Strong absorbance of UV light

Guanine

Nucleoside H oHoH oHoH H o CH 2 o Nitrogenous base A purine/pyrimidine + deoxyribose or ribose H oHoH H o CH 2 o N o N NH 2 Cytosine ‘ ‘ ‘ ‘ ‘ N-glycosidic linkage 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!

Deoxyribonucleic acid DNA is a nucleotide polymer linked by a 3’ to 5’ phosphodiester bond O-P-O-P-O-P-OCH 2 1’ 2’ 3’ 4’ 5’ N o N NH 2 O OOO OOO H OH H OCH 2 1’ 2’ 3’ 4’ Nitrogenous base O O - O -P - 5’ 5’ phosphate 3’ hydroxyl

Single-stranded DNA: Has polarity Has a hydrophilic side Has a hydrophobic side

RNA versus DNA - Stability issues

Double-stranded DNA 1) Pair of DNA chains in an antiparallel arrangement 5’3’ 5’3’ 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

Picture of E. coli DNA outside of the cell

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