Nucleic Acid Structure

🟢 Lite — Quick Review (1h–1d)

Rapid summary for last-minute revision before your exam.

Nucleic acids are polynucleotides built from repeating nucleotide units. Each nucleotide = a nitrogenous base + a pentose sugar (ribose in RNA, 2′-deoxyribose in DNA) + a phosphate group linked through a 3′→5′ phosphodiester bond. A nucleoside is the molecule without phosphate (base + sugar only).

DNA is a double-stranded, antiparallel right-handed helix (B-form, 10 bp per turn, 0.34 nm rise per bp). Purines (adenine, guanine) pair with pyrimidines (thymine in DNA, uracil in RNA, cytosine) — A=T via 2 H-bonds and G≡C via 3 H-bonds.

Chargaff’s rule: %A = %T and %G = %C in double-stranded DNA.
Beer–Lambert: A = ε · c · l — quantifies nucleic acids at 260 nm.
Tm (Wallace): 2°C(A+T) + 4°C(G+C) for short oligos.

🟡 Standard — Regular Study (2d–2mo)

Standard content for students with a few days to months.

Nucleotide chemistry

A nucleotide = nitrogenous base + pentose sugar + 1–3 phosphate groups. Removing the phosphate leaves a nucleoside (e.g., adenosine, deoxycytidine). The sugar–phosphate backbone carries a negatively charged phosphate at every linkage, giving nucleic acids their acidic character and uniform directionality: each strand runs 5′→3′, with the 5′-end bearing a free phosphate and the 3′-end a free hydroxyl.

Base pairing and helix geometry

Complementary base pairing is the heart of nucleic acid structure. Two hydrogen bonds hold A=T; three hydrogen bonds hold G≡C, which is why GC-rich regions melt at higher temperatures. B-DNA is right-handed with:

Parameter	Value
Base pairs per turn	10
Rise per base pair	0.34 nm (3.4 Å)
Helix pitch	3.4 nm
Grooves	Major (wider) and minor

The two strands are antiparallel (one 5′→3′, the other 3′→5′), and base stacking (hydrophobic + van der Waals) provides more helical stability than the H-bonds themselves.

Quantitation and melting

DNA concentration is measured by A260 using Beer–Lambert. When duplex DNA denatures, stacked bases unstack and absorbance rises by 30–40% — the hyperchromic effect, the basis of Tm measurement. Wallace’s rule (Tm = 2(A+T) + 4(G+C)) applies to oligos <14 nt; longer duplexes use the Marmur–Schildkraut equation.

Common FMGE traps

Confusing nucleoside (no phosphate) with nucleotide (has phosphate).
Writing that DNA and RNA both contain thymine — RNA has uracil instead.
Forgetting the 2′-OH on ribose is the structural reason DNA (2′-deoxyribose) is chemically more stable.

🔴 Extended — Deep Study (3mo+)

Comprehensive coverage for students on a longer study timeline.

Conformations and topoisomers

Beyond the canonical B-DNA, duplexes adopt A-form (right-handed, found in RNA·RNA and RNA·DNA hybrids, 11 bp/turn, 0.28 nm rise) and Z-form (left-handed, zig-zag backbone, favoured by alternating CG repeats in high-salt). Closed circular DNA is further modulated by supercoiling: positive supercoiling overwinds, negative supercoiling underwinds; topoisomerases I and II/gyrase relax this strain, a target of fluoroquinolones and cancer chemotherapy.

Worked example — DNA quantitation

A double-stranded DNA sample diluted 1:50 gives A260 = 0.660 in a 1 cm cuvette. Using the dsDNA extinction coefficient (ε260 ≈ 6,600 L·mol⁻¹·cm⁻¹ for expressing per nucleotide, or 50 µg/mL for 1.0 A260):

Concentration in undiluted sample = 0.660 × 50 µg/mL × 50 = 1,650 µg/mL (≈ 1.65 mg/mL).
Purity check: A260/A280 should be ~1.8 for pure dsDNA; protein contamination lowers this ratio.

High-yield distinctions

Feature	DNA	RNA
Sugar	2′-deoxyribose	Ribose (2′-OH)
Bases	A, G, C, T	A, G, C, U
Strands	In most keys double	In most keys single (with hairpins)
Stability	Higher (no 2′-OH)	Lower (alkali-labile)
Function	Genome storage	mRNA, tRNA, rRNA, regulatory RNAs

Two practice prompts

A 12-mer oligo has 4 A, 3 T, 2 G, 3 C. Using Wallace’s rule, calculate Tm = 2(7) + 4(5) = 34 °C.
Predict which melts first: a duplex with 60% GC or one with 40% GC — the higher-GC duplex has more triple H-bonds and stronger stacking, so it melts at the higher temperature.

Exam strategy

FMGE in standard papers places 1–2 MCQs on this topic. Memorise the H-bond count (A=T=2, G≡C=3), the 2′-deoxyribose vs ribose distinction, the 5′→3′ directionality, and Chargaff’s ratios. For numericals, keep Beer–Lambert units straight: ε in L·mol⁻¹·cm⁻¹, l in cm, c in mol·L⁻¹.

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Nucleic Acid Structure