Topic 6: Nucleic acids and protein synthesis
6.1 Structure of nucleic acids and replication of DNA
Students should be able to:

1) describe the structure of nucleotides, including the phosphorylated nucleotide ATP (structural formulae are not expected)

2) state that the bases adenine and guanine are purines with a double ring structure, and that the bases cytosine, thymine and uracil are pyrimidines with a single ring structure (structural formulae for bases are not expected)

3) describe the structure of a DNA molecule as a double helix, including: • the importance of complementary base pairing between the 5′ to 3′ strand and the 3′ to 5′ strand (antiparallel strands) • differences in hydrogen bonding between C–G and A–T base pairs • linking of nucleotides by phosphodiester bonds

4) describe the semi-conservative replication of DNA during the S phase of the cell cycle

5) describe the structure of an RNA molecule, using the example of messenger RNA (mRNA)

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1. Structure of Nucleotides (including ATP)

A nucleotide is the basic monomeric unit of nucleic acids such as DNA and RNA. Each nucleotide is composed of three components: a phosphate group, a five-carbon (pentose) sugar, and a nitrogenous base. The sugar is either deoxyribose (in DNA) or ribose (in RNA). The phosphate group is negatively charged and gives nucleic acids their acidic properties, while the nitrogenous base determines the identity of the nucleotide. Nucleotides are linked together by phosphodiester bonds between the phosphate of one nucleotide and the sugar of the next, forming a sugar–phosphate backbone.

A particularly important phosphorylated nucleotide is adenosine triphosphate (ATP). ATP consists of the nitrogenous base adenine, the sugar ribose, and three phosphate groups attached in a chain. The bonds between the phosphate groups are high-energy bonds; when ATP is hydrolysed to ADP (adenosine diphosphate) and inorganic phosphate, energy is released to drive metabolic processes such as active transport, muscle contraction, and biosynthesis. ATP therefore serves as the universal energy currency of the cell.

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2. Purines and Pyrimidines

The nitrogenous bases found in nucleotides fall into two categories based on their molecular structure. Purines, which have a double-ring structure, include adenine (A) and guanine (G). Pyrimidines, which have a single-ring structure, include cytosine (C), thymine (T), and uracil (U). Thymine is found only in DNA, while uracil replaces thymine in RNA. The difference in ring structure allows complementary base pairing to occur in DNA and RNA, as purines always pair with pyrimidines to maintain uniform width between the strands of the nucleic acid molecule.

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3. Structure of DNA

A DNA molecule consists of two antiparallel polynucleotide strands coiled around each other to form a double helix. Each strand has a sugar–phosphate backbone with nitrogenous bases projecting inward. The bases on one strand form hydrogen bonds with complementary bases on the opposite strand — adenine pairs with thymine via two hydrogen bonds, while cytosine pairs with guanine via three hydrogen bonds. This complementary base pairing ensures accurate replication and coding of genetic information.

The strands run in opposite directions — one from 5′ to 3′ and the other from 3′ to 5′ — a feature known as antiparallel orientation. Nucleotides are linked within each strand by phosphodiester bonds between the phosphate of one nucleotide and the 3′ hydroxyl group of the sugar of the next. The double helix is stable yet capable of unzipping for replication or transcription when hydrogen bonds are broken.

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4. Semi-Conservative Replication of DNA

During the S phase of the cell cycle, DNA replicates by a semi-conservative mechanism, meaning each new DNA molecule consists of one original (parental) strand and one newly synthesised strand. The process begins when the two DNA strands unwind and separate as the hydrogen bonds between base pairs are broken. Each strand acts as a template for the synthesis of a new complementary strand.

DNA polymerase adds complementary nucleotides to the exposed bases on the template strand, catalysing the formation of phosphodiester bonds between adjacent nucleotides. Because DNA polymerase can only add nucleotides in the 5′ to 3′ direction, replication is continuous on one strand (the leading strand) and discontinuous on the other (the lagging strand), which forms short fragments called Okazaki fragments. These fragments are later joined by DNA ligase, which seals the sugar–phosphate backbone to form a complete strand. This precise replication ensures genetic continuity between cells.

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5. Structure of RNA (mRNA as an example)

RNA (ribonucleic acid) is a single-stranded polynucleotide that contains the sugar ribose instead of deoxyribose, and the base uracil (U) instead of thymine. Messenger RNA (mRNA) is the RNA molecule that carries genetic information from DNA in the nucleus to ribosomes in the cytoplasm for protein synthesis. mRNA is synthesised by transcription from a DNA template strand and contains a sequence of codons — groups of three bases — each coding for one amino acid. Because mRNA is single-stranded and relatively short-lived, it allows genes to be expressed when needed and then degraded after translation.

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6.2 Protein Synthesis

Students should be able to:

1) state that a polypeptide is coded for by a gene and that a gene is a sequence of nucleotides that forms part of a DNA molecule

2) describe the principle of the universal genetic code in which different triplets of DNA bases either code for specific amino acids or correspond to start and stop codons

3) describe how the information in DNA is used during transcription and translation to construct polypeptides

4) state that the strand of a DNA molecule that is used in transcription is called the transcribed or template strand and that the other strand is called the non-transcribed strand

5) explain that, in eukaryotes, the RNA molecule formed following transcription (primary transcript) is modified by the removal of non-coding sequences (introns) and the joining together of coding sequences (exons) to form mRNA 

6) state that a gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide

7) explain that a gene mutation is a result of substitution or deletion or insertion of nucleotides in DNA and outline how each of these types of mutation may affect the polypeptide produced

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1. Genes and Polypeptides

A gene is a specific sequence of nucleotides on a DNA molecule that contains the coded information required to produce a particular polypeptide (or functional RNA). The sequence of bases in the gene determines the sequence of amino acids in the resulting polypeptide, which ultimately determines the protein’s structure and function. Therefore, the genetic code stored in DNA is expressed through the synthesis of proteins.

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2. The Universal Genetic Code

The genetic code is a set of rules that determines how the sequence of bases in DNA (or RNA) corresponds to specific amino acids in a polypeptide. The code is universal — the same triplets of bases correspond to the same amino acids in almost all organisms — reflecting common evolutionary origins. Each group of three bases, called a triplet (or codon in mRNA), codes for a specific amino acid. Some codons act as start codons (e.g., AUG, which also codes for methionine) or stop codons (e.g., UAA, UAG, UGA), which signal the end of translation. The code is also degenerate, meaning that most amino acids are coded for by more than one codon, reducing the effect of mutations.

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3. Transcription and Translation

Transcription occurs in the nucleus. The enzyme RNA polymerase binds to a specific region at the start of a gene on the DNA and unwinds the double helix. One strand acts as the template (transcribed) strand, and complementary RNA nucleotides pair with the exposed bases following base-pairing rules (A with U, C with G). RNA polymerase catalyses the formation of phosphodiester bonds between the RNA nucleotides, producing a primary mRNA transcript. The mRNA then detaches and leaves the nucleus through a nuclear pore to the cytoplasm.

Translation occurs at the ribosomes. The mRNA attaches to a ribosome, and transfer RNA (tRNA) molecules, each carrying a specific amino acid, align their anticodons with complementary codons on the mRNA. The ribosome moves along the mRNA, catalysing the formation of peptide bonds between adjacent amino acids. As the ribosome continues, a polypeptide chain is built up until a stop codon is reached, where the completed polypeptide is released and folds into its functional three-dimensional structure.

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4. Template and Non-Template Strands

In transcription, the template strand (also known as the transcribed strand) is the DNA strand that is used as a pattern for building the mRNA molecule. The other strand, called the non-template (non-transcribed) strand, has the same base sequence as the mRNA (except that thymine in DNA is replaced by uracil in RNA). Identifying which strand is the template is essential for understanding gene orientation and direction of transcription.

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5. RNA Processing in Eukaryotes

In eukaryotic cells, the RNA molecule formed immediately after transcription is called the primary transcript or pre-mRNA. This molecule contains both exons (coding sequences) and introns (non-coding sequences). Before it can be translated, the pre-mRNA must undergo RNA splicing, during which introns are removed and exons are joined together to form the mature mRNA. Additional modifications such as the addition of a 5′ cap and a poly-A tail may also occur to protect the mRNA from degradation and facilitate ribosome binding.

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6. Gene Mutations

A gene mutation is a change in the sequence of base pairs in a DNA molecule. This alteration can affect the genetic code and may result in the production of an altered polypeptide, which can lead to changes in the structure and function of the protein. Mutations occur spontaneously during DNA replication or may be induced by mutagenic agents such as radiation or certain chemicals.

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7. Types of Gene Mutation and Their Effects

• Substitution mutations occur when one base is replaced by another. This may result in a silent mutation (no change in amino acid), a missense mutation (a different amino acid inserted, possibly altering protein function), or a nonsense mutation (a stop codon introduced prematurely, leading to a truncated polypeptide).

• Insertion mutations involve the addition of one or more extra bases into the sequence, while deletion mutations remove one or more bases. Both can cause a frameshift mutation, altering the triplet reading frame and changing every amino acid downstream of the mutation. This often produces a completely non-functional protein.

The effect of a mutation depends on its type, location within the gene, and whether it alters critical regions of the protein.

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