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Nucleic Acids and Genetics A Language of Its Own. DNA Structure and Replication. In the mid-1900s, scientists knew that chromosomes, made up of DNA ( deoxyribonucleic acid ) and proteins , contained genetic information.
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DNA Structure and Replication • In the mid-1900s, scientists knew that chromosomes, made up of DNA (deoxyribonucleic acid) and proteins, contained genetic information. • However, they did not know whether the DNA or the proteins was the actual genetic material.
Various reseachers showed that DNA was the genetic material when they performed an experiment with a T2 virus. By using different radioactively labeled components, they demonstrated that only the virus DNA entered a bacterium to take over the cell and produce new viruses.
The Structure of DNA In the early 1950s, Rosalind Franklin and her associates began to test X-ray beams with DNA. The X-ray scattering produces a pattern that provides important clues to the structure of many molecules. This X-ray diffraction photograph of DNA was taken by Franklin. The X-shaped pattern in the center indicates that the structure of DNA is helical.
Structure of DNA • The structure of DNA was determined by James Watson and Francis Crick in the early 1950s. • DNA is a polynucleotide; nucleotides are composed of a phosphate, a sugar, and a nitrogen-containing base. • DNA has the sugar deoxyribose and four different bases: adenine (A), thymine (T), guanine (G), and cytosine (C).
Watson and Crick showed that DNA is a double helix in which A is paired with T and G is paired with C. This is called complementary base pairing because a purine (A and G) is always paired with a pyrimidine (T and C).
When the DNA double helix unwinds, it resembles a ladder. The sides of the ladder are the sugar-phosphate backbones, and the rungs of the ladder are the complementary paired bases. The two DNA strands are anti-parallel – they run in opposite directions.
Replication of DNA • DNA replication occurs during chromosome duplication; an exact copy of the DNA is produced with the aid of DNA polymerase. • Hydrogen bonds between bases break and enzymes “unzip” the molecule. • Each old strand of nucleotides serves as a template for each new strand.
New nucleotides move into complementary positions are joined by DNA polymerase. The process is semiconservative because each new double helix is composed of an old strand of nucleotides from the parent molecule and one newly-formed strand. Some cancer treatments are aimed at stopping DNA replication in rapidly-dividing cancer cells.
RNA • RNA (ribonucleic acid) is a single-stranded nucleic acid in which A pairs with U (uracil) while G pairs with C. • Three types of RNA are involved in gene expression: messenger RNA (mRNA) carries genetic information to the ribosomes, ribosomal RNA (rRNA) is found in the ribosomes, and transfer RNA (tRNA) transfers amino acids to the ribosomes, where the protein product is synthesized.
Two processes are involved in the synthesis of proteins in the cell: Transcription makes an RNA molecule complementary to a portion of DNA. Translation occurs when the sequence of bases of mRNA directs the sequence of amino acids in a polypeptide.
The Genetic Code • DNA specifies the synthesis of proteins because it contains a triplet code: every three bases stand for one amino acid. • Each three-letter unit of an mRNA molecule is called a codon. • Most amino acids have more than one codon; there are 20 amino acids with a possible 64 different triplets. • The code is nearly universal among living organisms.
Central Concept • The central concept of genetics involves the DNA-to-protein sequence involving transcription and translation. • DNA has a sequence of bases that is transcribed into a sequence of bases in mRNA. • Every three bases is a codon that stands for a particular amino acid.
Transcription • During transcription in the nucleus, a segment of DNA unwinds and unzips, and the DNA serves as a template for mRNA formation. • RNA polymerase joins the RNA nucleotides so that the codons in mRNA are complementary to the triplet code in DNA.
Translation • Translation is the second step by which gene expression leads to protein synthesis. • During translation, the sequence of codons in mRNA specifies the order of amino acids in a protein. • Translation requires several enzymes and two other types of RNA: transfer RNA and ribosomal RNA.
Transfer RNA • During translation, transfer RNA (tRNA) molecules attach to their own particular amino acid and travel to a ribosome. • Through complementary base pairing between anticodons of tRNA and codons of mRNA, the sequence of tRNAs and their amino acids form the sequence of the polypeptide.
Ribosomal RNA • Ribosomal RNA, also called structural RNA, is made in the nucleolus. • Proteins made in the cytoplasm move into the nucleus and join with ribosomal RNA to form the subunits of ribosomes. • A large subunit and small subunit of a ribosome leave the nucleus and join in the cytoplasm to form a ribosome just prior to protein synthesis.
A ribosome has a binding site for mRNA as well as binding sites for two tRNA molecules at a time. As the ribosome moves down the mRNA molecule, new tRNAs arrive, and a polypeptide forms and grows longer. Translation terminates once the polypeptide is fully formed; the ribosome separates into two subunits and falls off the mRNA. Several ribosomes may attach and translate the same mRNA, therefore the name polyribosome.
Review of Gene Expression • DNA in the nucleus contains a triplet code; each group of three bases stands for one amino acid. • During transcription, an mRNA copy of the DNA template is made. • The mRNA is processed before leaving the nucleus. • The mRNA joins with a ribosome, where tRNA carries the amino acids into position during translation.
Gene Mutations • A gene mutation is a change in the sequence of bases within a gene. • Frameshift Mutations • Frameshift mutations involve the addition or removal of a base during the formation of mRNA; these change the genetic message by shifting the “reading frame.”
Point Mutations • The change of just one nucleotide causing a codon change can cause the wrong amino acid to be inserted in a polypeptide; this is a point mutation. • In a silent mutation, the change in the codon results in the same amino acid.
If a codon is changed to a stop codon, the resulting protein may be too short to function; this is a nonsense mutation. If a point mutation involves the substitution of a different amino acid, the result may be a protein that cannot reach its final shape; this is a missense mutation. An example is Hbswhich causes sickle-cell disease.
Cause and Repair of Mutations • Mutations can be spontaneous or caused by environmental influences called mutagens. • Mutagens include radiation (X-rays, UV radiation), and organic chemicals (in cigarette smoke and pesticides). • DNA polymerase proofreads the new strand against the old strand and detects mismatched pairs, reducing mistakes to one in a billion nucleotide pairs replicated.
Cancer: A Failure of Genetic Control • Cancer is a genetic disorder resulting in a tumor, an abnormal mass of cells. • Carcinogenesis, the development of cancer, is a gradual process. • Cancer cells lack differentiation, form tumors, undergo angiogenesis and metastasize. • Cancer cells fail to undergo apoptosis, or programmed cell death.
Origin of Cancer • Mutations in at least four classes of genes are associated with the development of cancer. • 1) The nucleus has a DNA repair system but mutations in genes for repair enzymes can contribute to cancer. • 2) Mutations in genes that code for proteins regulating structure of chromatin can promote cancer.
3) Proto-oncogenes are normal genes that stimulate the cell cycle and tumor-suppressor genes inhibit the cell cycle; mutations can prevent normal regulation of the cell cycle. 4) Telomeres are DNA segments at the ends of chromosomes that normally get shorter and signal an end to cell division; cancer cells have an enzyme that keeps telomeres long.
Chapter Summary • Since DNA is the genetic material, its structure and functions constitute the molecular basis of inheritance. • Because the DNA molecule is able to replicate, genetic information can be passed from one cell generation to the next. • DNA codes for the synthesis of proteins; this process also involves RNA.
In eukaryotes, the control of gene expression occurs at all stages, from transcription to the activity of proteins. Gene mutations vary; some have little effect but some have a dramatic effect. Loss of genetic control over genes involved in cell growth and/or cell division cause cancer.
