Nucleic Acids and Genetics A Language of Its Own

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Nucleic Acids and GeneticsA Language of Its Own
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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.

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• 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.

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Viral DNA is labeled
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Viral capsid is labeled
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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.
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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).

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One pair of bases
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• 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).

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• 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.

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DNA double helix
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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.

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• 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.

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Overview of DNA replication
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Ladder configuration and DNA replication
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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.

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Structure of RNA
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• 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.

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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.

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Messenger RNA codons
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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.

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Overview of gene expression
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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.

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Transcription and mRNA synthesis
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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.

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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.

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Transfer RNA amino acid carrier
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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.

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• 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.

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Polyribosome structure and function
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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.

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Gene expression
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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.

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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.

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• 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 Hbs which causes sickle-cell
  disease.

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Sickle-cell disease in humans
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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.

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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.

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Cancer cells
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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.

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• 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.

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Causes of cancer
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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.

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• 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.