[MOD1LEC] Genes, Cell Division

What are the four main phases of the cell cycle?

• G1 - first gap phase; cell is growing and playing its typical metabolic roles

• S - synthesis phase where DNA is replicated

• G2 - second gap phase; growth and preparation for mitosis

• M - mitotic phase where the cell divides. This phase contains prophase, metaphase, anaphase, telophase, and cytokinesis

G1 through G2 is termed interphase

Meiosis

The cell division of s*x cells (egg and sperm)

• Two divisions occur

• Results in four daughter cells unique from the original

• Daughter cells contain 23 single chromosomes

Mitosis

The cell division of somatic cells (non-sex cells)

• One division occurs

• Results in two daughter cells identical to the original

• Daughter cells contain 23 pairs of chromosomes

Mitosis accounts for the growth of all tissues after birth, the replacement of dead cells, and the repair of damaged tissues

What are traits of normal cell division distinct from cells affected by cancer?

Contact inhibition - cells cease dividing when they come into contact with other cells

Cell cycle - normal cells only divide after a proper cell cycle has occurred and when they are mature

Mortality - normal cells only divide around 50 times and then they die via apoptosis

• Cancer cells divide infinitely as long as they are provided nutrients

Cell surface - normal cells “stick” together to form tissues, while cancer cells tend to “round-up”

• This enables metastasis to occur, where the cancer cells break off and spread throughout the body

Prophase [Phases Of Mitosis]

The stage where chromosomes condense

• The nuclear envelope breaks down

• Spindle fibers grow from centrioles

• Centrioles migrate to opposite poles of the cell

Metaphase [Phases Of Mitosis]

The stage where chromosomes line up along the equator or midline of the cell

• Some spindle fibers attach to the chromosomes

• Shorter microtubules form the aster and attach to the plasma membrane

Anaphase [Phases Of Mitosis]

The stage where sister chromatids separate as spindle fibers pull chromatids to opposite poles of the cell

• Each pole (each side of the cell) now has an identical set of genes

• Each pole and its contents will become a genetically identical daughter cell

Telophase [Phases Of Mitosis]

The end of nuclear division

• Chromosomes gather at each pole of the cell

• Chromosomes decondense and turn back into chromatin

• A new nuclear envelope appears at each pole

• New nucleoli appear in each nucleus

Cytokinesis [Phases Of Mitosis]

The stage where the cytoplasm is divided into two distinct cells so that each daughter cell has some

• The forming of the cleavage furrow occurs at the equator of the cell

Once the daughter cells have been formed, they return to interphase, specifically G1, or the phase where they are performing their normal metabolic functions

Gene

An information-containing segment of DNA

• Codes for the production of a molecule of mRNA

• mRNA goes on to synthesize one or more proteins

• The amino acid sequence of a protein is determined by a nucleotide sequence in the DNA

The genome

46 human chromosomes come in two sets, where humans receive one set of 23 from each parent

• All the DNA in one 23-chromosome set is called the human genome

• The human genome consists of about 3.1 billion nucleotide pairs

Human Genome Project (HGP)

A project carried out from 1990 to 2003 which provided society with knowledge of the base sequence (A, T, C, G) of more than 99% of the genome

Genomics

The comprehensive study of the whole genome and how its genes and noncoding DNA interact to affect the structure and function of the whole organism

• Genes average about 3,000 bases long, but range up to 2.4 million bases

• All humans, worldwide, are at least 99.99% genetically identical

  • Even the 0.01% variation means that we can differ from one another in more than 3 million base pairs

• Before the HGP, we know the chromosomal locations of fewer than 100 disease-producing mutations. We now know more than 1,400

DNA replication

The double helix of DNA is unzipped and unwound, and each original strand acts as a template for the replication of a new partner strand. Nucleotides are matched to synthesize the new partner strands into two new double helixes

• The new double helixes contain an old strand and the new copied strand

• DNA replication is semiconservative, meaning that each strand in an unzipped double helix will act as a template for synthesis of a new, complementary strand

New DNA is made by enzymes called DNA polymerases

The genetic code

The body can make millions of different proteins from just the same 20 amino acids

The genetic code is a system that enables these 4 nucleotides to code for the amino acid sequences of all proteins

Base triplets (found in DNA) » Codons (copy of DNA turned into mRNA) » Amino acids » Proteins

The genetic code is expressed in terms of codons

Stop codons

The signal to the protein-synthesizing machinery inside of a cell that it has reached the end of the chain of codons

• UAG, UGA, UAA are all stop codons

• AUG serves as a code for methionine and is a start codon

What is protein synthesis?

How DNA and different types of RNA collaborate to produce proteins

• The genetic code in DNA specifies which proteins a cell can make

• All of the body’s cells except the s*x cells and some immune cells contain identical genes

Different genes are activated in different cells. For example, genes for digestive enzymes are active in the stomach and pancreas cells but not in muscle cells; any given cell only uses one-third to two-thirds of its genes, while the rest remain dormant

What is a simplified version of protein synthesis?

When a gene has been activated, a messenger RNA is created (a mirror of the gene)

• Transcription - the step from DNA to mRNA that occurs in the nucleus

• Translation - the step from mRNA to protein synthesis. Most translation occurs in the cytoplasm

mRNA

Carries the genetic code from the nucleus to the cytoplasm

• mRNA is synthesized in the nucleus and acquires a protein cap that lets it leave the nucleus

• DNA is too large to leave the nucleus, so a small mRNA copy is created so it can leave through a nuclear pore

An enzyme called RNA polymerase binds to the DNA and assembles the RNA. Certain distinctive base sequences (often TATATA or TATAAA) inform the polymerase of where to begin

tRNA

Binds to a free amino acid floating around in the cytosol and delivers it to a ribosome to be added to a growing protein chain

• One loop of the molecule includes an anticodon, or a series of three nucleotides complementary to a specific codon of mRNA

• The first tRNA to bind to a ribosome at the start of translation is called the initiator tRNA

The anticodon determines what the mRNA says and then gives it an amino acid corresponding to that base triplet

Ribosomes

“Reading machines” found in the cytosol that are made up of a small subunit and a large subunit

• Each is composed of several enzymes and rRNA

• The two subunits only come together during the translation of mRNA

• The tRNA binds to the A site, then the P site, then the E site of the ribosome

Protein processing and secretion

• Protein synthesis is NOT finished when its amino acid sequence (primary structure) has been assembled

• To be functional, it must coil or fold into precise secondary and tertiary structures

• In some cases, it associates with other protein chains (quaternary structure)