DNA-RNA

• pyrimidine ring
• imidazole ring (like a histidine amino acid)

• Bases differ in terms of theside chains off of the rings.
• The key sidechains are either amine (NH2), Oxy (=O) or methyl (CH3).
• The nitrogens and oxygensgive lots of sites for hydrogen bonding (tohold things together)

- The "core" nitrogenous bases found in DNA and RNA can be modified with different side chains, etc. into "unusual"bases

• - Base modifications seen often include
• 1- Methylation
• 2- Acetylation
• 3- Glycosylation
• 4- Reduction (i.e. change a keto to an alcohol; change a double bond to a single bond)

-Example tRNA contain a high amount of unusual bases (e.g. dihydrouracil) and Pseudouridine

• viral DNA and
• transferRNAs (tRNA) or
• certain regions of DNA
• help to regulate how that site is recognized by
• 1- nucleic acid binding factors and/or
• 2- hydrolyzed by nucleic acid cleaving enzymes            (like proteases but with nucleic acid targets)

• Having a much higher phosphorus content
• Resistant to proteolysis
• Composed of sugars, phosphate and nitrogen (now
• called bases)

• Nucleoside (Furanose Sugar + Nitrogenous Base)
• Nucletide (Nucleoside + Phosphate)

• the amount of adenine (A) = thymine (T),
• the amount of guanine (G) = cytosine (C)
• (A + G) = (C + T)

- phosphate groups, which bind the 3' end of one sugar to the 5' end of the next sugar

• Pyrimidines (T, C, U): C1  (the Nitrogen that will bond with ribose sugar )
• Purines (A, G): C1 is the nitrogen in the pyridine ring furthest removed from that nitrogen in the imidazole ring which will bind with ribose in a nucleoside

• The key sugar molecule of DNA and RNA is ribose
• Ribose is a 5 carbon sugar with a furanose ring

• DNA: has Deoxyribose (H in position 2)
• RNA: has Ribose (OH in position 2)

• Because it is more prone to hydrolysis.
• The “extra” hydroxy (electronegative) pulls electrons away from the carbon to the oxygen, making the ribose ring more susceptible to hydrolysis by OH groups

• The nitrogenous bases will covalently bond to C1’ of ribose or deoxyribose
• The location of C3’ and C5’ – these are the linkage sites that of polymerized nucleic acids

AMP (Adenosine Monophosphate)

ADP (Adenosine Diphosphate)

Adenosine Triphosphate (ATP)

• The phosphates confer a negative charge on the nucleotide.
• These groups add protons (H+) to the environment, making it acidic
• Hence, Nucleotides are known as “nucleic acids”

• 1- They serve as sources of chemical energy (ATP & GTP)
• 

- They participate in cellular signaling as secondary messengers (cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP)

- They are incorporated into important cofactors of enzymatic reactions (Coenzyme A, FAD, FMN, NAD+ and NADP+)

• -They also serve as carriers of activated intermediates in the synthesis of some carbohydrates (UDP-glucose glycogen), lipids (CDP-choline phosphatidylcholine)
• and conjugated proteins (glycoproteins UDP-galactose; GDP-mannose)
• ex, glucose, you have to add energy by adding phosphate to make energy, that is why We need UDP
• - You have to energize these molecules by use necleotides
• Nucleotides can also be key regulatory compounds that can inhibit or activate key enzymes to drive or otherwise direct metabolic pathways

- The removal of the “oxy” at 2’-carbon uses an enzyme called Ribonucleotide Reductase (which “reduces” the carbon-oxygen bond by adding hydrogens)

- Ribonucleotide reductase uses an important cofactor –Thioredoxin – which contributes two sulfhydril groups (SHs) to drive the reaction.

- Thioredoxin gets “recycled” (reduced back to 2 free –SH groups) by NADPH + H +

• - Ribonucleotide Reductase is a key enzyme for controlling
• the supply of deoxyribonucleotides (and hence for controlling cell replication)
• 

- Hydroxyurea reduces production of deoxyribonucleotides by inhibiting Ribonucleotide Reductase.

• - Hydroxyurea is used in the treatment of cancers like chronic myelogenous leukemia and in treating sickle cell disease
• - Hydroxyurea reduces production of deoxyribonucleotides by inhibiting Ribonucleotide Reductase.
• 

• 5 end have free phophate 
• 3 end have free hydroxyl- not attached to other nucleotides

• Phosphodiester bonds from 3-5 direction
• Bases written in sequence from 5-3

• Hydrolytically by chemicals, or
• Hydrolyzed enzymatically by family of nucleases
• (deoxyribonucleases for DNA and ribonucleases for RNA)

Pentamidine analog drug

• Nucleotide Base Pairing - Driven by and Stabilized by Hydrogen bonds
• Hydrophobic pi (p)-stacking due to the aromatic nature of the nitrogenous bases, while hydrophilic basses are outside

• 1- Changing the pH of the solution, or by
• 2- Heating
• The DNA will “melt” (denature) when sufficient heat is added. This is called the “melting temperature”
• The phosphodiester bonds are maintained (are NOT broken) by heating.
• When the DNA is cooled, it will re-form the double strand,This is called "renaturation or reannealing"

• The B-form 
•          (righ-handes helix- 10 nucleotide- 360⁰turn)
•           seen in DNA complexes
• The A form
•           (right-handed helix- 11 nucleotide)
•           form from partially dehydration of B-form
•           seen in DNA-RNA and RNA-RNA complexes
•  The Z form
•            (left-handed helix- 12 base pairs)
•             seen in deoxyribophophate backbone

• - In the nucleus of eukaryote.
• Linear dsDNA+ histon proteins= chromatin

• - In the mitochnondria
• dsDNA form a closed circular molecule

• - In prokaryotic 
• supercoiled DNA+ non- histone protein= nucleoid

• - In bacteria 
• small, circular, 
• extra-chromosomal DNA molecules called plasmids.
• Plasmids carry genetic information and can replicate independently of chromosomes

• DNA is present in chromosomes in the nucleus and in the mitochondria of eukaryotic cell
• - DNA+histone= chromatin------chromosome

• The flow of information from DNA to RNA to Protein
• The Master Plan” for an organism is stored in the DNA
• RNA, however, that translates the information into working molecules that “carry out” the master plan
• 

The sequence of bases in DNA will define where transcription enzymes

RNA polymerases enzymes will regulate which areas of DNA to transcribe, , where to start , how much of the DNA to transcribe and where to stop transcription

• All three types of RNA are unbranched polymeric molecules
• Composed of nucleoside monophosphates
• Linked by phosphodiester bonds

• Having Ribose, rather than Deoxyribose sugar
• Having Uracil instead of Thiamine
• Existing as a Single Strand that folds back on itself into complex structures

• Synthesize rRNA 
• Assemble ribosomes

Ribosome

Ribozyme

Carries the genetic information from the nuclear DNA to the cytosol (where protein synthesis occurs)

Polycistronic: the message for more than one protein is included in a single mRNA (prokaryotes and viruses)

• mRNA contain added 5’ “ends” and 3’ “ends” that are not turned into proteins.
• The 3’ end is covered with a long sequence of adenine bases (a “poly A tail”).
• The 5” end has a cap, and often has a leader sequence that helps the synthesized protein sequester into subcellular organelles and fold properly

Each coding sequence has its own starting and ending region

Sometimes, the message for more than one protein is included in a single mRNA (often seen in prokaryotes and viruses)

• tRNAs are also synthesized as long precursors that must be shortened by ribonucleases
• Modifications include:
• Removing sequences from both the 5’ and the 3’ ends
• Removing an “intron” from the spot where the anti-codon loop will form
• Adding a –CCA sequence to the 3’ end of tRNA (at the spot where the amino acids will be “carried”)
• Reducing certain Uracil structures to make Dihydrouracil; rearranging the way bases are linked to the riboses (i.e. Pseudouridine)

• - The first “processing” reaction is to put a “Cap” on the 5’ end.
• - The cap is a Methylated Guanosine triphosphate that is placed “backwards” on the 5’ terminal ribose 

• - Next, add a poly-Adenosine (Poly-A) tail to the 3’ end of mRNA. From 40-200 “A”s are
• added after transcription is finished (post-transcription).