DNA - Structure, Salient Features, and Types

INTRODUCTION

PART 1: CHEMICAL STRUCTURE OF DNA (Building Blocks)

Each Nucleotide Has 3 Parts:

How Nucleotides Are Joined:

PART 2: WATSON-CRICK DOUBLE HELIX MODEL (Secondary Structure)

Figure: DNA double helix - Lippincott Illustrated Reviews: Biochemistry, 8th ed.

Key Points of the Double Helix:

1. Two strands coil around a common central axis (the helical axis) - like a twisted ladder.
2. Antiparallel orientation - one strand runs 5'→3' and the other runs 3'→5' (in opposite directions).
3. Backbone is on the outside - the sugar-phosphate (deoxyribose-phosphate) backbone is hydrophilic and faces outward.
4. Bases are on the inside - the hydrophobic nitrogenous bases are stacked inward (like steps of a ladder).
5. Base pairing (Chargaff's Rule):
   • A pairs with T (Adenine - Thymine) → 2 hydrogen bonds
   • G pairs with C (Guanine - Cytosine) → 3 hydrogen bonds
   • So A = T and G = C in any double-stranded DNA. The total purines always equal total pyrimidines.
6. Major and minor grooves - Because of the helical twist, two unequal grooves form along the surface:
   • Major groove (wide) - where most regulatory proteins and transcription factors bind.
   • Minor groove (narrow) - where some drugs (e.g., dactinomycin/actinomycin D) intercalate.
7. Right-handed helix - the helix turns in a clockwise direction (called right-handed).
8. 10.4 base pairs per turn of the helix, with a rise of 3.4 Å (angstroms) per base pair, and a full turn every 34 Å.

PART 3: SALIENT FEATURES OF DNA

PART 4: TYPES OF DNA

Figure: Z, B, and A forms of DNA - Basic Medical Biochemistry, 6th ed.

1. B-DNA (Most Important)

• The normal form found in cells under physiological (water-rich) conditions.
• Right-handed double helix.
• 10.4 bp per turn (approximately 10 bp per turn).
• Rise per base pair: 3.4 Å.
• Has clear major and minor grooves.
• This is the Watson-Crick model.

2. A-DNA

• Found when DNA is in low humidity (dehydrated conditions) or in DNA-RNA hybrid molecules.
• Also right-handed, but more compact and wider.
• 11 bp per turn.
• Rise per base pair: 2.3 Å (shorter/more compact than B-form).
• Has a deeper major groove.

3. Z-DNA

• Left-handed helix (turns counter-clockwise) - the opposite of A and B forms.
• Named "Z" because the phosphate backbone zigzags (zigs and zags in a Z-shaped pattern).
• 12 bp per turn (approximately 11-12 bp).
• Rise per base pair: 3.8 Å.
• Narrower and more elongated.
• Found transiently in cells during transcription (RNA synthesis).
• Physiological role is still being studied.

Comparison Table: Types of DNA

ADDITIONAL NOTE: Linear vs Circular DNA

• Eukaryotes - linear dsDNA in nucleus (organized into chromosomes with histone proteins); circular dsDNA in mitochondria.
• Prokaryotes - single, circular dsDNA molecule in the nucleoid.
• Plasmids - small, circular, extrachromosomal DNA in bacteria (used in genetic engineering).

QUICK MEMORY TRICK

"All Bankers Get Tired" = A bonds T, G bonds C (base pairing rule) B-DNA = Body (normal), A-DNA = compact (like A for Altered), Z-DNA = Zigzag (left-handed)

tRNA (Transfer RNA) - Structure and Function

INTRODUCTION

PART 1: STRUCTURE OF tRNA

Basic Facts:

• tRNA is a single-stranded RNA molecule.
• Length: 74 to 95 nucleotides long.
• Sedimentation coefficient: 4S (smallest RNA).
• Contains many unusual (modified) bases - e.g., Dihydrouracil (D), Pseudouracil (ψ), Inosine, Ribothymidine.
• Makes up about 15-20% of total cellular RNA.
• There is at least one tRNA for each of the 20 amino acids. In humans, there are at least 50 different tRNA species.

Secondary Structure: THE CLOVERLEAF

Figure: tRNA cloverleaf structure showing amino acid attachment at 3' end (ACC/CCA) and anticodon loop pairing with mRNA codon - Lippincott Illustrated Reviews: Biochemistry, 8th ed.

3D (Tertiary) Structure: L-SHAPE

• The acceptor arm is at one end of the L.
• The anticodon loop is at the other end of the L.
• These two important functional ends are kept far apart - one binds the amino acid, the other reads the mRNA.

Figure: Mature tRNA (cloverleaf) showing the CCA-3' acceptor end, modified bases (yellow), and anticodon loop - Lippincott Illustrated Reviews: Biochemistry, 8th ed.

Key Structural Features to Remember:

1. 3' end always = -CCA-OH (universal, added post-transcriptionally by enzyme nucleotidyltransferase)
2. 5' end always = phosphate group
3. Contains modified/unusual bases (not found in other RNA types)
4. Extensive intrachain base pairing - holds the cloverleaf shape

PART 2: FUNCTIONS OF tRNA

1. Adaptor Molecule (Most Important Function)

2. Carries Amino Acids ("Charging" of tRNA)

• Each tRNA is charged (loaded) with its specific amino acid by an enzyme called Aminoacyl-tRNA Synthetase.
• There are 20 different synthetase enzymes - one for each amino acid.
• The amino acid attaches by ester bond to the 3'-OH of the CCA end (acceptor arm).
• This process requires ATP.
• A tRNA with an amino acid attached = Charged tRNA (aminoacyl-tRNA).
• A tRNA without an amino acid = Uncharged tRNA.

3. Reads the mRNA Code (Anticodon-Codon Pairing)

• The anticodon in the anticodon loop of tRNA is a 3-base sequence.
• It pairs with the complementary codon on mRNA in an antiparallel direction.
• Example: If mRNA codon = AUG (codes for Methionine), then tRNA anticodon = UAC.

4. Delivers Amino Acid to Ribosome

• The charged tRNA carries the amino acid to the ribosome.
• At the ribosome, the amino acid is added to the growing polypeptide chain.
• After releasing the amino acid, the tRNA leaves the ribosome as uncharged tRNA.

5. Proofreading

• Aminoacyl-tRNA synthetases also have proofreading (editing) activity - they remove a wrongly attached amino acid, ensuring accuracy of protein synthesis.

SUMMARY TABLE

QUICK MEMORY TRICK

"tRNA = Taxi RNA"

• Picks up passenger (amino acid) at the CCA-3' end
• Reads the address (anticodon pairs with mRNA codon)
• Drops off passenger at ribosome for protein building

Genetic Code

INTRODUCTION

WHAT IS A CODON?

• The genetic code is a triplet code - every 3 consecutive nucleotide bases on mRNA = 1 codon.
• Each codon codes for one specific amino acid (or a stop signal).
• Total possible codons: 4³ = 64 codons (4 bases taken 3 at a time).
• These 64 codons code for only 20 amino acids + stop signals.

THE CODON TABLE

Figure: The Genetic Code Table - Lippincott Illustrated Reviews: Biochemistry, 8th ed.

Start Codon:

• AUG = codes for Methionine (Met) = the START/Initiation codon for all proteins.
• Every protein begins with Methionine (though it may be removed later).

Stop Codons (Termination Codons):

• UAA - "Ochre"
• UAG - "Amber"
• UGA - "Opal" (also called "Umber")
• These 3 stop codons do NOT code for any amino acid. They signal the ribosome to stop making the protein.
• So: 61 codons code for 20 amino acids, and 3 codons are stop signals.

PROPERTIES / CHARACTERISTICS OF THE GENETIC CODE

1. TRIPLET CODE (Three-letter code)

• Each codon consists of 3 nucleotide bases (a triplet).
• Example: AUG, GCU, UAA
• A sequence of 3 bases = 1 amino acid.

2. DEGENERATE (Redundant)

• Most amino acids are coded by more than one codon.
• Example: Leucine is coded by 6 codons (UUA, UUG, CUU, CUC, CUA, CUG).
• Only Methionine (AUG) and Tryptophan (UGG) have just 1 codon each.
• The third base of the codon (3' end) is the one that usually varies - this is called "wobble position".
• This degeneracy protects the organism - a mutation in the third base often still codes for the same amino acid.

3. UNAMBIGUOUS (Specific)

• Each codon codes for only ONE specific amino acid - never two.
• The same codon never means two different amino acids.
• AUG always = Methionine. Never anything else.
• Remember: Degenerate = one amino acid can have many codons. Unambiguous = one codon has only one meaning.

4. NON-OVERLAPPING

• Codons do NOT share bases with each other.
• The mRNA is read 3 bases at a time, one after the other, without overlap.
• Example: AUGCCUGAA is read as: AUG | CCU | GAA (not AUG, UGC, GCC...)

5. COMMALESS (No punctuation)

• There are no gaps or "commas" between codons on the mRNA.
• Reading starts at a fixed point (AUG) and continues continuously without skipping, until a stop codon is reached.
• This fixed reading order is called the Reading Frame.

6. UNIVERSAL

• The genetic code is the same in ALL living organisms - bacteria, plants, animals, humans.
• AUG means Methionine in a bacterium and in a human cell.
• This is why genetic engineering works - human insulin gene placed in E. coli bacteria still produces human insulin!
• Exception: Mitochondria use a slightly different code. For example, UGA codes for Tryptophan in mitochondria (instead of being a stop codon).

7. POLAR (Read in one direction only)

• mRNA is always read 5' → 3' direction.
• Codons are always written from 5' end to 3' end.

MUTATIONS AND THE GENETIC CODE

SUMMARY TABLE: Properties of Genetic Code

QUICK MEMORY TRICK

"The Genetic Code is DUNDUC"

• Degenerate
• Unambiguous
• Non-overlapping
• Direction: 5'→3'
• Universal
• Commaless

• Clear numbered points
• Simple language
• Neat tables
• Diagrams described simply
• Exactly the style Indian MBBS exams expect

DNA - Structure, Salient Features and Types

(As per Satyanarayana Biochemistry - 1st Year MBBS)

INTRODUCTION

• DNA is the genetic material of the cell - it stores and transmits hereditary information.
• It is present in the nucleus (chromosomes), mitochondria, and in prokaryotes (nucleoid region).
• DNA was first isolated by Friedrich Miescher in 1869 from pus cells.
• Its double helical structure was proposed by Watson and Crick in 1953 - one of the greatest discoveries in biology.

PART I: CHEMICAL COMPOSITION (Building Blocks of DNA)

Each Nucleotide Has 3 Components:

Memory tip: "Pure As Gold" = Purines = Adenine + Guanine

How Nucleotides Join:

• Nucleotides are joined by 3'→5' Phosphodiester bonds
• The phosphate of one nucleotide links to the 3'-OH of the next
• This forms a long unbranched chain with a free 5' end and a free 3' end

PART II: STRUCTURE OF DNA - WATSON AND CRICK MODEL (B-DNA)

1. Chargaff's rules of base pairing
2. X-ray crystallography data from Rosalind Franklin and Maurice Wilkins

The Double Helix - Key Points:

• DNA has two polynucleotide strands coiled around a common central axis (helical axis)
• The overall shape resembles a twisted ladder (spiral staircase)

• The two strands run in opposite directions
• One strand goes 5'→3' and the other goes 3'→5'
• This is called antiparallel arrangement

• The deoxyribose-phosphate backbone (hydrophilic) is on the outside of the helix
• Like the two side rails of a ladder

• The nitrogenous bases (hydrophobic) are stacked on the inside
• Like the steps of a ladder
• Bases are perpendicular to the helical axis

• Bases on one strand pair with bases on the opposite strand:
  • A pairs with T → connected by 2 Hydrogen bonds
  • G pairs with C → connected by 3 Hydrogen bonds
• This means: A = T and G = C in any double-stranded DNA
• Total Purines = Total Pyrimidines

Memory tip: "AT - Two bonds (2)", "GC - Three bonds (3)" → AT home, Get Cozy with Three

• Due to the helical twisting, two grooves are formed on the surface:
  • Major groove (wide) - where regulatory proteins and enzymes bind
  • Minor groove (narrow) - where some drugs intercalate (e.g., Actinomycin D)

• The helix turns clockwise when viewed from above
• This is called a right-handed helix

PART III: SALIENT FEATURES OF DNA (Watson-Crick B-DNA)

PART IV: TYPES OF DNA

Figure: Three forms of DNA - Z, B, and A (Lippincott Biochemistry, 8th ed.)

1. B-DNA

• The most common form found in cells under normal (physiological) conditions
• Right-handed helix
• 10 bp per turn
• Rise per bp = 3.4 Å
• Has clear major and minor grooves
• This is the Watson-Crick model - the one you always study

2. A-DNA

• Found in dehydrated (low water) conditions
• Also found in DNA-RNA hybrid molecules
• Right-handed helix (same as B, but different dimensions)
• 11 bp per turn
• Rise per bp = 2.3 Å (shorter, more compact)
• Wider and shorter than B-DNA
• Deeper major groove

3. Z-DNA

• Left-handed helix (turns counter-clockwise - opposite to A and B)
• Named "Z" because the phosphate backbone zigzags in a Z-pattern
• 12 bp per turn
• Rise per bp = 3.8 Å (longer, more stretched)
• Narrow and elongated
• Found transiently during active transcription (RNA synthesis)
• Less common; stabilized by specific Z-DNA binding proteins

Comparison Table - Types of DNA

Memory tip for handedness: "B is for Body (normal/right)", "Z is for Zigzag (left)"

ADDITIONAL IMPORTANT POINTS

Linear vs. Circular DNA:

• Eukaryotes: Linear DNA in nucleus (bound to histone proteins → chromatin → chromosomes); Circular DNA in mitochondria
• Prokaryotes: Single circular DNA in nucleoid (no membrane)
• Plasmids: Small circular DNA in bacteria (used in genetic engineering)

Stabilization of DNA Double Helix:

1. Hydrogen bonds between complementary base pairs (A-T and G-C)
2. Base stacking interactions (hydrophobic interactions between stacked bases inside the helix)
3. Ionic interactions between negatively charged phosphate groups and positive ions (Mg²⁺, histones)

EXAM DIAGRAM - WATSON-CRICK DOUBLE HELIX

Figure: Watson-Crick double helix - showing all major structural features (Lippincott Biochemistry, 8th ed.)

• 5' end and 3' end of both strands (antiparallel)
• Deoxyribose-phosphate backbone (outside)
• A=T and G≡C base pairs (inside)
• Major groove and minor groove
• Helical axis
• 3.4 Å between base pairs, 34 Å per turn

QUICK SUMMARY FOR RAPID REVISION

DNA = Double helix, Antiparallel, Complementary base pairing (A=T, G≡C), Right-handed (B-form), 10 bp/turn, 3.4 Å rise, Major + Minor grooves

3 Types: B (normal, right-handed) → A (compact, right-handed) → Z (Zigzag, LEFT-handed)

• Watson-Crick Double Helix Model
• Types of DNA (A, B, Z forms)
• Salient features of DNA

• Nucleotides, nucleosides
• Purines and pyrimidines
• Phosphodiester bonds

• DNA Replication (semi-conservative)
• DNA Repair mechanisms
• Transcription (DNA → RNA)

• Chargaff's rules
• Denaturation and renaturation of DNA
• Supercoiling of DNA
• Chromatin structure and histones
• Mitochondrial DNA

• DNA vs RNA
• Prokaryotic vs Eukaryotic DNA

Purines and Pyrimidines

(1st Year MBBS - Biochemistry)

INTRODUCTION

• They contain Nitrogen atoms in their rings
• They are basic (slightly alkaline) in nature

PART I: PURINES

What are Purines?

• Purines have a DOUBLE RING structure
• One ring is a pyrimidine ring (6-membered) fused with an imidazole ring (5-membered)
• They are larger molecules

Purine Bases:

Memory tip: "Pure As Gold" = Purines = Adenine + Guanine

PART II: PYRIMIDINES

What are Pyrimidines?

• Pyrimidines have a SINGLE RING structure (6-membered ring only)
• They are smaller molecules

Pyrimidine Bases:

Memory tip: "CUT the PY" = Cytosine, Uracil, Thymine = PYrimidines

STRUCTURES OF BASES (Must know for exam)

Figure: Chemical structures of purines (Adenine, Guanine) and pyrimidines (Thymine, Cytosine, Uracil) - Lippincott Illustrated Reviews: Biochemistry, 8th ed.

Key Structural Points:

• Adenine = Purine with an amino group (-NH₂) at position 6
• Guanine = Purine with a keto group (=O) at position 6 and amino group at position 2
• Thymine = Pyrimidine with a methyl group (-CH₃) at position 5 (this is what makes it different from Uracil)
• Cytosine = Pyrimidine with an amino group (-NH₂) at position 4
• Uracil = Pyrimidine like Thymine but without the methyl group - only found in RNA

Important: Thymine = Uracil + one methyl group (-CH₃)

PART III: NUCLEOSIDES

Nucleoside = Base + Sugar (NO phosphate)

Two types of sugar:

• Ribose (has -OH at 2' carbon) → used in RNA
• Deoxyribose (has only -H at 2' carbon, no -OH) → used in DNA

PART IV: NUCLEOTIDES

Nucleotide = Base + Sugar + Phosphate

ATP (Adenosine Triphosphate) = the energy currency of the cell - a nucleotide!

PART V: COMPARISON TABLE - PURINES vs PYRIMIDINES

PART VI: BASE PAIRING IN DNA (Very Important!)

• Adenine (Purine) pairs with Thymine (Pyrimidine) → 2 Hydrogen bonds
• Guanine (Purine) pairs with Cytosine (Pyrimidine) → 3 Hydrogen bonds

Note: G-C pair is stronger than A-T pair because 3 H-bonds > 2 H-bonds. DNA with more G-C content has a higher melting temperature (Tm)

PART VII: UNUSUAL (MODIFIED) BASES

• Dihydrouracil (D) - in tRNA
• Pseudouracil (ψ) - in tRNA
• Inosine - in tRNA (anticodon)
• 5-Methylcytosine - in DNA (gene silencing/methylation)
• 7-Methylguanosine - the cap of eukaryotic mRNA

QUICK SUMMARY FOR EXAM

Memory Tricks:

• "Pure Gold" = PURines = Adenine + Guanine
• "CUT the PY" = PYrimidines = Cytosine + Uracil + Thymine
• "AT 2, GC 3" = A-T has 2 H-bonds, G-C has 3 H-bonds
• Thymine = only in DNA | Uracil = only in RNA