17.1 Molecular Structure of DNA & RNA

Molecular Structure of DNA & RNA

Quick Answer: Genetic material is built from nucleotides, each made of a pentose sugar, a nitrogenous base, and a phosphate. DNA is a double-stranded, antiparallel, right-handed helix; RNA is usually single-stranded and substitutes uracil for thymine. The PA-CAT Bulletin of Information, rev. 20240815 lists "Molecular Structure and Replication of Genetic Material" as the first grouping within the Genetics content area, so nucleotide chemistry and base-pairing logic are fair game for the 26 Genetics items.

Nucleotide Architecture

A nucleotide has three covalently joined parts: a pentose (five-carbon) sugar, a nitrogenous base, and a phosphate group. A nucleotide minus the phosphate is a nucleoside; the distinction (nucleoside vs. nucleotide) is a common PA-CAT vocabulary item.

The nitrogenous base bonds to the sugar's 1′ carbon through an N-glycosidic bond; the phosphate bonds to the 5′ carbon. The carbons of the pentose are numbered 1′ through 5′, and this numbering defines strand polarity. Purines (A, G) are double-ring; pyrimidines (C, T, U) are single-ring. A purine always pairs with a pyrimidine, keeping the helix a constant ~2.0 nm diameter.

Nucleotides polymerize through phosphodiester bonds linking one nucleotide's 5′ phosphate to the next nucleotide's 3′ hydroxyl, releasing pyrophosphate. This gives every strand a defined 5′→3′ polarity: one end carries a free 5′ phosphate, the other a free 3′ hydroxyl. By convention, sequences are always written 5′→3′.

The DNA Double Helix

Watson and Crick's 1953 model, built on Rosalind Franklin's X-ray diffraction "Photograph 51," describes DNA as a right-handed double helix with two antiparallel strands. Key structural facts the PA-CAT may test:

• Antiparallel orientation: one strand runs 5′→3′, the partner 3′→5′, so the 5′ end of one strand faces the 3′ end of the other.
• Sugar–phosphate backbone is on the exterior; bases project inward and stack like rungs of a ladder, ~0.34 nm between adjacent bases.
• Complementary base pairing: A pairs with T via 2 hydrogen bonds; G pairs with C via 3 hydrogen bonds. G–C-rich regions are harder to melt (higher Tm) because the extra H-bond stabilizes the helix.
• Chargaff's rules: %A = %T and %G = %C in double-stranded DNA. If a sample is 30% adenine, it must be 30% thymine, leaving 40% split equally as 20% G and 20% C. This rule applies only to double-stranded DNA; single-stranded viral genomes violate it.
• One full helical turn ≈ 3.4 nm (10 base pairs in B-DNA); the major groove and minor groove spiral around the helix and provide protein-binding sites where transcription factors read the base sequence.
• B-DNA is the physiological form; A-DNA is dehydrated; Z-DNA is a left-handed zig-zag form found at some regulatory regions.

Denaturation, Renaturation, and Hybridization

Heat or high pH breaks the hydrogen bonds between strands, causing denaturation (melting). The melting temperature (Tm) is the temperature at which half the DNA is single-stranded; Tm increases with G–C content. Slow cooling allows complementary strands to reanneal — renaturation. Renaturation of mixed single-stranded DNA from two sources is hybridization, the basis of PCR primers, Southern blots, and fluorescent in situ hybridization (FISH).

RNA Structure and the Three Principal RNAs

RNA is usually single-stranded but folds back on itself to form local double-stranded stems and loops, giving tRNA its cloverleaf and rRNA its complex tertiary fold. The 2′-OH makes RNA chemically more labile than DNA and enables some RNAs to act as catalysts (ribozymes). Three RNAs dominate gene expression:

1. Messenger RNA (mRNA) — carries the codon sequence from DNA to the ribosome. In eukaryotes, primary transcript (pre-mRNA) is processed: a 7-methylguanosine 5′ cap is added, introns are spliced out by the spliceosome, and a poly-A tail is added at the 3′ end before nuclear export. Prokaryotic mRNA is generally polycistronic (one transcript → several proteins).
2. Transfer RNA (tRNA) — the adaptor molecule. Each tRNA is ~75–90 nucleotides, folds into a cloverleaf, and carries a three-nucleotide anticodon at one end and a specific amino acid esterified to its 3′ CCA terminus at the other. Aminoacyl-tRNA synthetases charge each tRNA with the correct amino acid — there is one synthetase per amino acid.
3. Ribosomal RNA (rRNA) — the structural and catalytic core of the ribosome. The large subunit's rRNA is the peptidyl transferase that catalyzes peptide-bond formation; ribosomes are thus ribozymes, supporting the RNA-world hypothesis.

Additional small RNAs regulate expression: snRNAs form the spliceosome; miRNAs (~22 nt) silence mRNAs via the RNA-induced silencing complex (RISC); snoRNAs guide rRNA chemical modification.

Why Structure Matters for the PA-CAT

The Bulletin groups "Molecular Properties of Genes" and "Molecular Structure and Replication of Genetic Material" separately. Expect questions that ask you to (1) distinguish DNA from RNA by sugar and base, (2) apply Chargaff's rules to compute base composition, (3) identify which RNA carries codons (mRNA) vs. anticodons (tRNA), and (4) predict which strand is the template vs. the coding strand given a gene orientation. A common distractor confuses thymine and uracil; remember uracil appears only in RNA in normal cells, and thymine only in DNA. Another frequent trap: a G–C-rich segment melts at a higher, not lower, temperature than an A–T-rich segment.