Structure of nucleic acids

1. Overview

Nucleic acids are the information-carrying molecules of the cell. There are two types: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Both are polymers built from nucleotide monomers. DNA stores the genetic code as a stable, antiparallel double helix, while RNA, such as messenger RNA (mRNA), is a single strand used to carry and use that information. This section explains the structure of a nucleotide (including the energy-carrying nucleotide ATP), the difference between purine and pyrimidine bases, how nucleotides join to build DNA and RNA, and how DNA is copied accurately by semi-conservative replication.

Key Definitions

• Nucleotide: the monomer of a nucleic acid, made of a pentose (5-carbon) sugar, a phosphate group and a nitrogenous base joined together.
• Purine: a nitrogenous base with a double-ring structure; adenine and guanine are purines.
• Pyrimidine: a nitrogenous base with a single-ring structure; cytosine, thymine and uracil are pyrimidines.
• Complementary base pairing: the rule that adenine pairs with thymine (or uracil in RNA) and cytosine pairs with guanine, joined by hydrogen bonds.
• Antiparallel: describes the two strands of a DNA molecule running in opposite directions, one 5 prime to 3 prime and the other 3 prime to 5 prime.
• Phosphodiester bond: the covalent bond formed in a condensation reaction that links the phosphate of one nucleotide to the sugar of the next, forming the sugar-phosphate backbone.
• Semi-conservative replication: copying of DNA in which each new molecule contains one original parent strand and one newly made strand.
• DNA polymerase: the enzyme that adds free nucleotides to a template strand, building a new strand only in the 5 prime to 3 prime direction.
• DNA ligase: the enzyme that joins adjacent DNA fragments on the lagging strand by forming phosphodiester bonds in the sugar-phosphate backbone.
• Messenger RNA (mRNA): a single-stranded molecule that carries a copy of the base sequence of a gene from the nucleus to the ribosomes.
• Gene: a sequence of nucleotides that codes for the amino acid sequence of a particular polypeptide.

Content

Structure of a nucleotide

A nucleotide is made of three parts joined together by condensation reactions:

• a pentose sugar (a 5-carbon sugar) — deoxyribose in DNA and ribose in RNA;
• a phosphate group; and
• a nitrogenous base (adenine, guanine, cytosine, thymine or uracil).

The phosphate group is attached to the 5′ carbon of the sugar and the base is attached to the 1′ carbon. Many nucleotides linked together form a polynucleotide. (You do not need the structural formulae of these molecules.)

ATP — a phosphorylated nucleotide

ATP (adenosine triphosphate) is a nucleotide used as the cell's immediate energy currency. It has the same basic plan as any nucleotide but with three phosphate groups instead of one. Its structure is therefore: the base adenine, the pentose sugar ribose, and three phosphate groups in a chain. Energy is released when the bond to the outermost phosphate is hydrolysed, forming ADP and an inorganic phosphate.

Purines and pyrimidines

The five bases fall into two groups based on the number of rings in the molecule:

• Purines have a double-ring structure: adenine (A) and guanine (G).
• Pyrimidines have a single-ring structure: cytosine (C), thymine (T) and uracil (U).

In base pairing, a purine always pairs with a pyrimidine. This keeps the two strands of DNA an even distance apart, giving the helix a constant width. (Structural formulae for the bases are not expected.)

Structure of DNA: the double helix

A DNA molecule is made of two polynucleotide strands coiled into a double helix. Within each strand, the sugar of one nucleotide is joined to the phosphate of the next by a phosphodiester bond (formed by condensation), creating a sugar-phosphate backbone on the outside of the helix. The bases project inwards.

The two strands are antiparallel: one runs in the 5′ to 3′ direction and the other runs in the opposite 3′ to 5′ direction. The strands are held together by hydrogen bonds between complementary bases, following strict pairing rules:

• A pairs with T by two hydrogen bonds;
• C pairs with G by three hydrogen bonds.

Because C–G pairs have one extra hydrogen bond, regions rich in C–G are held together more strongly, so more energy is needed to separate them.

Complementary base pairing is the key to DNA's role: the base sequence of one strand exactly determines the sequence of the other, so each strand can act as a template to make an accurate new copy.

Semi-conservative replication

DNA is copied during the S phase of the cell cycle by semi-conservative replication. "Semi-conservative" means each new double helix keeps (conserves) one original strand and has one newly synthesised strand.

The main steps are:

1. The hydrogen bonds between the two strands break, so the double helix unwinds and unzips into two single strands. Each acts as a template.
2. Free DNA nucleotides line up against their complementary bases on each template strand (A with T, C with G).
3. DNA polymerase catalyses the formation of phosphodiester bonds between adjacent nucleotides, building each new strand. Crucially, DNA polymerase can only add nucleotides in the 5′ to 3′ direction.
4. The result is two identical DNA molecules, each containing one parent strand and one new strand.

Leading and lagging strands

Because the two template strands are antiparallel and DNA polymerase only works in the 5′ to 3′ direction, the two new strands are made differently:

• The leading strand is built continuously, in one piece, because its template lets DNA polymerase move in the same direction as the helix is unwinding.
• The lagging strand is built discontinuously, in short fragments, because its template runs the "wrong way" for the enzyme.

To understand why the lagging strand needs fragments, follow the logic step by step:

• DNA polymerase can add nucleotides only in the 5′ to 3′ direction.
• On the lagging-strand template, that direction points back towards the unwinding point, not away from it.
• So the enzyme can only copy a short stretch before it runs into the part it has already done. Each time the helix unwinds a little more and exposes a fresh section of template, the enzyme must return to the newly opened point and start a brand-new fragment, again working 5′ to 3′.
• This is why the lagging strand ends up as a series of separate short pieces rather than one continuous strand.

The short fragments of the lagging strand are then joined together by DNA ligase, which forms the phosphodiester bonds between the fragments to complete the sugar-phosphate backbone and make one continuous strand. (You are not expected to know the other enzymes involved or different types of DNA polymerase.)

Structure of RNA (using mRNA as the example)

Messenger RNA (mRNA) is a single-stranded molecule built from RNA nucleotides. It is made in the nucleus as a complementary copy of the base sequence of a gene and carries this coded information to the ribosomes, where it is used to direct the building of a polypeptide. Because it copies just one gene, an mRNA molecule is relatively short compared with a whole DNA molecule.

The table below summarises the key differences between DNA and mRNA — set out this way because "compare DNA and RNA" questions need matched, two-sided points:

Feature	DNA	mRNA
Number of strands	Double-stranded (double helix)	Single-stranded
Pentose sugar	Deoxyribose	Ribose
Bases used	A, T, C, G	A, U, C, G (uracil replaces thymine)
Relative length	Very long (whole chromosome)	Short (a copy of one gene)
Main role	Long-term store of genetic information	Carries the coded message from nucleus to ribosomes

Note that in mRNA the base uracil (U) takes the place of thymine, and uracil pairs with adenine.

Worked example

Exam-style question: DNA replication is described as semi-conservative and produces a leading strand and a lagging strand. Explain why one new strand is made continuously while the other is made in short fragments, and name the enzyme that joins the fragments. [3]

Model answer:

• The two template strands are antiparallel, so they run in opposite directions (one 5′ to 3′, the other 3′ to 5′).
• DNA polymerase can only add nucleotides in the 5′ to 3′ direction, so it builds the leading strand continuously but must build the lagging strand in short fragments, starting a new fragment each time more template is exposed.
• The fragments of the lagging strand are joined together by DNA ligase, which forms the phosphodiester bonds in the sugar-phosphate backbone.

Worked example

Exam-style question: A sample of double-stranded DNA is found to contain 28% adenine. Using complementary base pairing, calculate the percentage of thymine, cytosine and guanine in the sample. Then, for the template strand 5′-ATGCCGTA-3′, write out the complementary strand, showing its polarity. [4]

Model answer:

• Adenine always pairs with thymine, so thymine = 28%.
• Adenine + thymine together = $28 + 28 = 56\%$, so cytosine + guanine make up the remaining $100 - 56 = 44\%$.
• Cytosine pairs with guanine in equal amounts, so each is $44 \div 2 = 22\%$: cytosine = 22% and guanine = 22%.
• The complementary strand is antiparallel, so it runs in the opposite direction and each base is matched (A–T, C–G): the complement of 5′-ATGCCGTA-3′ is 3′-TACGGCAT-5′ (often written 5′-TACGGCAT-3′ reading the new strand in its own 5′ to 3′ direction).

Key Equations

This is a structural topic, so no equations are required; focus on describing structures, bonding and the steps of replication accurately.

Common Mistakes to Avoid

• Stating that DNA contains both thymine and uracil. Thymine is found in DNA; uracil replaces thymine in RNA. Each molecule has only one of the two.
• Mixing up the number of hydrogen bonds. Remember A–T has two hydrogen bonds and C–G has three — many students reverse these or give the wrong number.
• Calling phosphodiester bonds "hydrogen bonds" (or vice versa). Phosphodiester bonds are strong covalent bonds along the sugar-phosphate backbone; the two strands are held together by weaker hydrogen bonds between bases. Confusing them loses marks on both structure and replication questions.
• Forgetting to say the strands are antiparallel. Always state that the two strands run in opposite directions (5′ to 3′ and 3′ to 5′); this is the reason a lagging strand exists.
• Saying a purine pairs with a purine, or a base "matches" itself. A purine always pairs with a pyrimidine (A with T, C with G). Use the word complementary, not "same" or "matching".
• Describing replication as "conservative". In semi-conservative replication each new molecule keeps one original strand and gains one new strand — not two brand-new strands and not the whole original molecule kept intact.
• Being vague about what carries the code. When describing mRNA, state precisely that it carries a copy of the base sequence of a gene to the ribosomes, rather than describing it loosely as "a piece of DNA" or "a strand of genetic material".
• Defining a gene loosely as "a strand of DNA". A gene is a sequence of nucleotides that codes for the amino acid sequence of a particular polypeptide. Saying only "part of DNA" or "a length of DNA" misses the crucial point that the sequence carries coded instructions for a specific protein.

Exam Tips

• Learn the base pairs as a pair of facts: A–T (two H bonds) and C–G (three H bonds) — questions often ask you to link extra hydrogen bonding in C–G to greater stability.
• When describing a nucleotide, always name all three parts (pentose sugar, phosphate, nitrogenous base) to secure the marks. The same frame answers "describe the structure of ATP" — just swap to the specific parts: adenine, the sugar ribose and three phosphate groups.
• Use precise directional language: write 5′ to 3′ and 3′ to 5′ clearly, as the difference between leading and lagging strands depends on it.
• For "compare DNA and RNA" questions, give comparative points (e.g. "DNA is double-stranded whereas RNA is single-stranded"; "DNA contains deoxyribose whereas RNA contains ribose").
• In replication questions, name the enzymes correctly: DNA polymerase builds strands; DNA ligase joins fragments. Do not blur the two roles together.
• Use the word complementary when describing base pairing, and template when describing how one strand directs the making of another — these are the terms that earn marks.