DNA replication begins when protein complexes sequentially unwind the DNA into two strands. As this unwinding proceeds, new strands that are complementary to each of the single strands are synthesized. The enzyme DNA polymerase is responsible for this process, because it adds nucleotides that are complementary to the nucleotides of the original strand.
The addition of nucleotides is based on the two pairs being complementary: Adenine binds to thymine, and cytosine binds to guanine via hydrogen bonds. One end is called the 3' (three-prime) and the other the 5' (five-prime) end. DNA polymerase (see the upcoming section, “Coding for proteins: RNA and DNA”) synthesizes DNA directionally by adding the 5' end of a nucleotide to the free 3' end of a nascent DNA strand. Thus, the DNA strand is elongated in the 5' to 3' direction.
The cell cycle
The cell cycle is the process by which one parent cell divides into two daughter cells. This cycle involves both DNA replication and cell division. In eukaryotes, the phase when the cell is not dividing is called interphase. The division of the cell into two daughter cells occurs during mitosis, which is itself divided into different phases: prophase, metaphase, anaphase, and telophase. After telophase, cytokinesis occurs, which is the phase when the cytoplasm actually divides into two daughter cells.
Coding for proteins: RNA and DNA
Protein synthesis is the process by which cells generate proteins from the code in the DNA sequence. It occurs in several stages, including transcription from DNA to messenger RNA (mRNA), and translation, or the assembly of proteins by ribosomes using the mRNA template. (RNA is a nucleotide like DNA, except is has the nucleotide uracil substituted for thymine.) This section explores these stages.
The genetic code
The genetic code is a sequence of three nucleotides (called a codon) that specifies an amino acid. As I mention earlier in this chapter, four types of nucleotides exist, so a three-nucleotide sequence (such as ACT or TAG) with four choices at each position allows for 64 possible codons (or 43). However, only 20 amino acids are used to make proteins. Several different codons specify the same amino acid. This may sound redundant, and the concept is sometimes called degeneracy, but this degeneracy does have benefits. One benefit is that some mutations that change one of the nucleotides may not change which amino acid is produced — so the protein’s function won’t be compromised.
Transcription mechanisms
Transcription occurs in the cell nucleus. The transcription process “reads” the DNA code to create a matching messenger RNA molecular template that will exit the nucleus and be used to synthesize proteins. The RNA strand is complementary to the DNA strand, just like the two single DNA strands are complementary to each other in the double helix, except that in RNA the nucleotide uracil takes the place that thymine occupies in DNA.
In transcription, one strand of the DNA double helix — the template strand — is used to form the complementary mRNA sequence. The transcription process has three stages that are regulated by transcription factors and co-activators:
Initiation: In this first part of transcription, DNA is partially “unzipped” by the enzyme helicase, allowing access to the DNA nucleotide sequence for copying. Transcription factors bind the promoter region of the gene, which is a control region immediately preceding the beginning of the gene. Polymerase, the molecule that copies DNA into RNA, binds to a complex of transcription factors at the promoter.
Elongation: RNA polymerase unwinds the DNA double helix, moves down it, and elongates the RNA transcript by adding ribonucleotides in a 5' to 3' direction (refer to the earlier section, “DNA replication”). The RNA polymerase “reads” the DNA strand sequentially and produces a single strand of messenger RNA (complementary to the DNA sequence that is its template).
Termination: When the RNA polymerase reaches the end of the gene, the mRNA and polymerase detach from the DNA. The single strand of newly synthesized mRNA leaves the nucleus through nuclear pores and migrates into the cytoplasm.
Protein synthesis
The mRNA sequence is not usually directly translated into the amino acid sequence forming a protein. In eukaryotic cells, the mRNA (called primary transcript) undergoes post-transcriptional modification to yield what’s called heterophilic nuclear RNA (hnRNA). Spliceosomes (a combination of nucleoproteins and RNA molecules that help to splice) then remove the introns (noncoding parts of the gene) from the hnRNA. This produces the final mRNA — composed of the coding exons. (See the section “Introns versus exons,” later in this chapter.)
Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.
Regulating genes
Cells can modify the rate at which specific gene products (protein or RNA) are produced. This occurs as cells proceed down their developmental pathways, but it also occurs in response to environmental stimuli. Gene expression can be modified at all the stages of transcription, RNA processing, and post-translational protein modification.
One of the main mechanisms of regulating DNA expression is methylation by methyltransferase enzymes (adding methyl groups to adenine or cytosine nucleotides in the DNA), which occurs on cytosine nucleotides. Another important regulation mechanism is