bio 210 : 3B

Cell Cycle

• Interphase: When the cell grows and carries on its usual cellular activities.
• Cell division (mitosis and cytokinesis): When one cell divides to become two cells.

During Interphase

• Period from cell formation to cell division.
• Cell carries out normal metabolism (e.g., protein synthesis, cellular respiration).
• Cell also prepares for cell division.
• DNA is in its uncondensed, threadlike chromatin state.

Three Parts of Interphase

• G₁ (gap 1): Vigorous growth and metabolism of cell.
  • Cells that permanently cease dividing are said to be in $G{_0}$ phase (Muscle and Nervous Tissue).
• S (synthetic): DNA replication occurs.
• G₂ (gap 2): The cell continues preparation for division.

DNA Replication

• Occurs prior to cell division; the cell makes an exact copy of all nuclear DNA.
• Double-stranded DNA helices unwind and “unzip.”
• Each DNA strand acts as a template for a new complementary strand.
• DNA polymerase is the enzyme necessary to begin adding DNA nucleotides to complimentary bases.
• The nucleoplasm is the source of nucleotides for complementary base pairing ($A-T$) ($G-C$) to form a new strand.
• DNA polymerase synthesizes both new strands at one time.
• The end result is identical “daughter” DNA molecules formed from the original DNA strands.
• These replicated strands of DNA are connected by a centromere.
• The duplicated chromosome/duplicated DNA is called a sister chromatid.
• Each Sister Chromatid is a DNA molecule.
• Sister Chromatids are duplicated DNA molecules.
• Sister Chromatids are duplicated Chromosomes.
• During mitotic cell division, one complete copy of DNA will be given to each new cell.

Cell Division

• Most cells need to replicate continuously for growth purposes and/or repair purposes.
• Skeletal muscle cells, cardiac muscle cells, and nerve cells (neurons) do not divide efficiently.
  • These cells lose their ability to divide when mature, so damaged cells are replaced with scar tissue.

M (Mitotic) Phase

• Phase in which division consists of 2 distinct events:
  • Mitosis
  • Cytokinesis
• Mitosis (M phase): Division of the nucleus, and the duplicated DNA is distributed to new daughter cells.
• The four stages of mitosis ensure each cell receives a full copy of the replicated DNA.

Four Stages of Mitosis

1. Prophase:
   • Early prophase:
     • Chromatin condenses, forming visible chromosomes.
     • Each chromosome and its duplicate (sister chromatids) are held together by a centromere.
     • Centrioles begin synthesizing microtubules that push each centriole to opposite poles of the cell (mitotic spindle).
   • Late prophase:
     • Nuclear envelope breaks up.
     • Microtubules attach to centromeres and pull chromosomes to the center (equator) of the cell.
     • Unattached microtubules push against each other, causing cell poles to move farther apart.
2. Metaphase:
   • Centromeres of chromosomes align at the cell’s equator (“meet in middle”) along an imaginary plane midway between poles (metaphase plate).
3. Anaphase:
   • The shortest of all phases.
   • Sister chromatids are pulled apart.
   • Each sister chromatid now becomes a separate chromosome.
   • One chromosome of each original pair goes to opposite poles, and microtubules continue forcing poles apart.
   • Cytokinesis begins during anaphase.
4. Telophase:
   • Begins when chromosome movement stops.
   • Each set of chromosomes (at opposite ends of cell) uncoils to form chromatin.
   • New nuclear membranes form around each chromatin mass, nucleoli reappear, and spindle fibers disappear.
   • Cytokinesis continues through telophase.

Cytokinesis

• Begins during late anaphase and continues through telophase.
• A ring of actin microfilaments contracts to form a cleavage furrow that pinches the two daughter cells apart.

Protein Synthesis

• Proteins composed of polypeptide chains made up of amino acids.
• DNA is the master blueprint holding the code for protein synthesis and directing the order of amino acids sequence in a polypeptide.

Definitions of a Gene

• A segment of a DNA molecule that holds the code for the synthesis of one polypeptide (protein).
• A segment of a DNA molecule that holds the order of sequence of amino acids for the synthesis of a protein.
• A sequence of DNA nucleotides that code for the synthesis of a protein.

What is the Genetic Code?

• Rules by which the base sequence of a gene is translated from a nucleotide sequence on mRNA into an amino acid sequence of protein.
• Genetic code is the specific order of 3 nitrogen bases of mRNA that represents an amino acid.
• Three nitrogen bases of mRNA is a codon.

Definitions:

• 3 nucleotides on DNA: Called a triplet.

• 3 nucleotides on mRNA: Called a codon.

• 3 nucleotides on tRNA: Called an anticodon.

• Triplet, Codon, Anticodon all represent the same amino acid.

  • DNA Triplet, GGC, codes for amino acid proline.
  • mRNA Codon, CCG, codes for amino acid proline.

Gene Structure

• Genes are composed of exons and introns.
  • Exons: Part of gene that codes for amino acids. Exons exit the nucleus as mRNA.
  • Introns: Noncoding segments interspersed amongst exons. Introns remain inside the nucleus.

The Role of RNA in Protein Synthesis

• Remember:
  • Three nucleotides on DNA called a triplet = GGC
  • mRNA called a codon = CCG
  • tRNA called anticodon = GGC
  • All represent same amino acid proline.
• DNA cannot leave the nucleus.
• RNA is the “go-between” molecule that links DNA to proteins.
• mRNA copies DNA code (gene) in the nucleus and then mRNA carries the gene into cytoplasm to the ribosomes (site of protein synthesis).

Three Types of RNA:

1. Messenger RNA (mRNA): A single-stranded nucleotide that copies genetic code (gene) from the DNA template strand with RNA complementary base pairs, resulting in a strand of mRNA.
   • Remember: RNA differs from DNA in that uracil is substituted for thymine, and RNA has ribose instead of deoxyribose sugar.
   • Transcription: Occurs in the nucleus; copies the gene off DNA into a single strand of mRNA.
     • mRNA copies the triplet code from DNA with 3 nucleotides on mRNA called a codon.
     • The codon maintains triplet code from DNA.
2. Ribosomal RNA (rRNA): Structural component of ribosomes and the site of protein synthesis.
3. Transfer RNA (tRNAs): A carrier RNA for a specific amino acid.
   • tRNA has a special area that contains a specific anticodon.
   • Each tRNA can carry a specific amino acid that is coded for on the DNA’s triplet.

Translation

• Process where the anticodon of tRNA complementary base-pairs with the codon of mRNA at the rRNA (ribosome), and the tRNA drops off its specific amino acid to a growing polypeptide chain of the protein.

Protein Synthesis Occurs in Two Steps:

1. Transcription: Occurs in the nucleus where DNA’s triplet is coded into mRNA’s codon.
2. Translation: Occurs in the cytoplasm at the ribosome where mRNA is decoded from nucleotides by tRNA into amino acids, and the protein is assembled.

Transcription Process

• Transferring DNA gene base sequence (triplets) to complementary base sequence of mRNA (codons).
  • Triplet on DNA to codon on mRNA: $AAA \rightarrow UUU$ (phenylalanine).
• In transcription, the DNA gene segment is opened and exposed by RNA polymerase, an enzyme that synthesizes mRNA.
• RNA polymerase adds complementary nucleotides to the growing mRNA.

Three Phases of Transcription

1. Initiation: RNA polymerase separates DNA strands.
2. Elongation: RNA polymerase adds complementary nucleotides to growing mRNA, matching sequence on DNA template strand to complementary base pairing on mRNA ($A-U$ and $G-C$).
3. Termination: Transcription stops when RNA polymerase reaches a special termination signal code.

• Newly formed mRNA is called pre-mRNA and contains both introns and exons.
• Introns are removed from pre-mRNA, leaving only exon coding regions.
• mRNA is made up of exons that exit the nucleus.

Translation Process (Continued)

• The second step of protein synthesis.
• The language of nucleic acids is translated into the language of amino acids to form proteins.
• Involves mRNA, tRNA, rRNA (ribosome), genetic code, and sometimes the rough ER.

Genetic Code

• Contains 64 codons for only 20 amino acids.

• Some amino acids are represented by more than one codon; this redundancy helps protect against transcription errors.

• There is one start codon ($AUG = \text{methionine}$) and three stop codons ($UGA, UAG, UAA$).

• The rest of the codons code for amino acids.

• For example, the anticodon of tRNA (UAU) will complementary bind to the codon on mRNA (AUA) and drop off amino acid isoleucine.

• rRNA (ribosome) coordinates the coupling of mRNA and tRNA for tRNA drop-off of the AA.

Ribosomes has 3 binding sites for tRNA

• A-site (Aminoacyl): For incoming tRNA.
• P-site (Peptidyl): For tRNA dropping off the AA and forming the peptide bond.
• E-site (Exit): For outgoing tRNA.

Sequence of events in translation

1. Initiation: The ribosome scans mRNA looking for the first methionine codon (start codon - $AUG$).
   • When many ribosomes attach to the same mRNA, it is called a polyribosome because multiple ribosomes are attached to one mRNA, all producing multiple copies of the same protein.
2. Elongation: Amino acids are added one at a time to the growing polypeptide chain until a stop codon enters the A site.
3. Termination: One of three stop codons ($UGA, UAA, UAG$) on mRNA enters the A-site, and translation ends.

Role of Rough ER (RER) in protein synthesis

• A short amino acid segment present on a growing polypeptide chain signals the ribosome to dock on the rough ER surface.
• Once docked, the forming polypeptide enters RER.
• Once inside the RER, a sugar group may be added to the protein, the protein’s shape may be altered, and the protein is enclosed in a vesicle for transport to the Golgi apparatus.

Summary: From DNA to Proteins

• Transfer of genetic information goes from DNA triplets $\rightarrow$ Complementary base sequence of mRNA codons $\rightarrow$ tRNA base sequence of anticodons.
• DNA triplets are coded to mRNA codons.
• mRNA codons are base-paired with tRNA anticodons to ensure correct amino acid sequence.
• Anticodon sequence of tRNA is identical to DNA sequence, except uracil is substituted for thymine.

Apoptosis (programmed cell death)

• Disposes of unneeded or damaged cells.
• Causes certain cells to neatly self-destruct (e.g., cancer cells, infected cells, old cells).
• Cell shrinks and dies and is phagocytized by macrophages.

Autophagy (self-eating)

• Process of disposing of nonfunctional organelles and cytoplasmic bits by lysosomes.

Cell Destruction and Modified Rates of Cell Division