The Cell Cycle: Interphase and Mitotic Stage

The Cell Cycle

• An orderly set of stages occurs from eukaryotic cell's first division to when resulting daughter cells divide.
• The cell cycle has two major stages: interphase and mitotic stage.

Interphase

• Interphase is the longest part of the cell cycle, about 90%.
• It is divided into three stages: G1, S, and G2.
• During the G1 stage (Gap 1), the cell grows and doubles its organelles like mitochondria and ribosomes, and accumulates materials needed for DNA synthesis.
• Nerve and muscle cells remain in the G0 phase.
• During the S stage, DNA replication occurs, and all proteins associated with DNA are synthesized, the chromosomes are duplicated, and every chromosome is made of two identical chromatids.
• During the G2 stage, the cell synthesizes proteins like microtubule proteins that are necessary for division.
• A mammalian cell takes approximately 20 hours to complete this process.

Mitotic Stage

• This stage follows interphase.
• Mitosis refers to the division of the nucleus.
• Cytokinesis refers to the division of the cytoplasm.
• Results in two genetically identical daughter cells.

Control of the Cell Cycle

• A signal is a molecule that influences the activities of a cell.
• Internal and external signals control the cycle.
• External signals, such as growth factors, are signaling proteins received at the plasma membrane.
• Internal signals are a family of proteins called cyclins that increase and decrease as the cell cycle continues.
• Specific cyclins must be present for the cell to proceed from one stage to the next.
• Without cyclins, the cell cycle halts at G1, M, or G2 checkpoints.

Cell Cycle Checkpoints

• G1 checkpoint: p53 checks for damaged DNA and initiates DNA repair. If repair isn't possible, apoptosis results. RB checks nutrient availability.
• G2 checkpoint: Checks if DNA replication was properly completed or if DNA is damaged.
• M checkpoint: Checks for proper alignment of chromosomes and attachment to the mitotic spindle.

Apoptosis

• Programmed cell death is caused by enzymes called caspases.
• Caspases are controlled by inhibitors, but can be unleashed by internal or external signals.
• Cell division and apoptosis are opposing forces.
• Cell division increases the number of somatic cells, while apoptosis decreases it.
• These opposing processes keep the number of cells at an appropriate level.
• Cell division and apoptosis occur throughout our lifetimes to maintain the body's homeostasis.
• An abnormal cell that could become cancerous or a virus-infected cell are cells that die through apoptosis.
• Cells harbor caspase enzymes that are normally kept in check by inhibitors.
• Internal or external signals can unleash caspase enzymes.
• Signaling protein p53 stops the cell cycle at G1 when the cell's DNA is damaged.
• It initiates an attempt at DNA repair.
• If successful, the cycle continues to mitosis, if not, apoptosis is initiated.

The Eukaryotic Chromosome

• A chromosome consists of a single DNA molecule condensed in the cell by histone proteins.
• DNA + histones = Chromatin
• Nucleosome: DNA around 8 histones.
• Nucleosomes are joined by "linker" DNA.
• Euchromatin represents the active chromatin that can be transcribed by RNA polymerase and transcription factors.
• Heterochromatin is a more highly compacted form of the chromosome
• It's inactive chromatin, with genes that are hardly ever transcribed.
• Compact chromosomes are more easily moved than extended chromatin.

Mitosis and Cytokinesis

• Eukaryotic cell division involves Mitosis (nuclear division) and Cytokinesis (division of cytoplasm).
• Before mitosis begins, chromatin condenses (coils) into distinctly visible chromosomes.
• Each species has a characteristic chromosome number.

Eukaryotic Chromosomes

• Diploid (2n) number: in diploid cells there are 2 copies of each chromosome. Humans have 2n=46 chromosomes or 23 pairs.
• Haploid (n) number: only gametes (sperm and eggs) have only one of each pair of chromosomes with n=23.
• In the S phase, each chromosome replicates.
• Two genetically identical sister chromatids result attached at the centromere with a protein complex called Kinetochores.
• Each chromatid (daughter chromosome) goes to one daughter cell.

Mitosis in Animal Cells

• Centrosome: Microtubule organizing center of animal cell.
• Each centrosome contains two barrel shaped centrioles and has an aster.
• The centrosome organizes the mitotic spindle.
• The spindle contains many fibers, with each fiber being a cylindrical bundle of microtubules.
• Mitosis proceeds in 5 stages: prophase, prometaphase, metaphase, anaphase, telophase.

Mitosis Phases

• During prophase chromosomes condense, the nucleolus disappears, and the spindle starts to form.
• Early prophase is marked by duplicated centrosomes and chromatin condensing into chromosomes, with the nuclear envelope fragmenting.
• During prometaphase, the nuclear envelope fragments and spindle fibers attach to the chromosomes.
• During metaphase, chromosomes are aligned at the metaphase plate
• Centromeres of duplicated chromosomes are aligned at the metaphase plate.
• Kinetochore spindle fibers attached to the sister chromatids come from opposite spindle poles.
• During anaphase, sister chromatids part and travel to the spindle poles.
• Each pole recieves the same number of chromosomes as the parent cell.
• During telophase, daughter cells are formed as nuclear envelopes and nucleoli reappear.
• Chromosomes will become indistinct chromatin.

Cytokinesis in Animal Cells

• Cytokinesis is the division of the cytoplasm which produces two genetically identical daughter cells.
• Cleavage furrow deepens when a contractile ring of actin filaments forms a circular constriction between the two daughter nuclei.
• The contractile ring continues to separate until there are two independent daughter cells.

Mitosis and Cytokinesis in plant cells

• Mitosis in plants is similar to mitosis in animals.
• Plant cells lack centrioles and asters.
• Spindle still forms.
• In plant cells a rigid wall does not permit furrowing.
• Small flattened disks produced from Golgi apparatus appear between the two daughter plant cells as a cell plate.
• The cell plate eventually fuses.

Functions of Mitosis in Animal & Plant Cells

• Permits growth and repair.
• In flowering plants, meristematic tissue retains the ability to divide throughout the life of the plant.
• In mammals, mitosis is necessary when:
• A fertilized egg becomes an embryo
• An embryo becomes a fetus
• A cut heals or a broken bone mends

Reproductive & Therapeutic Cloning

• Stem cells: Retain the ability to divide.
• Ex: Red bone marrow stem cells divide to produce various types of blood cells.
• Reproductive cloning: To produce an individual that is genetically identical to the one that donated a nucleus.
• Therapeutic cloning: To produce specialized human tissues, either by using adult stem cells or embryonic stem cells.

The Cell Cycle and Cancer

• Abnormal growth of cells is called a tumor.
• Benign tumors are not cancerous. They are encapsulated and do not invade neighboring tissue or spread..
• Malignant tumors are cancerous.
• They are not encapsulated and readily invade neighboring tissues.
• May also detach and lodge in distant places which is known as metastasis.
• Results from mutation of genes regulating the cell cycle.
• Carcinogenesis: Development of cancer.
• Tends to be gradual and may take years before a cell is obviously cancerous.

Characteristics of Cancer Cells

• Cancer cells lack differentiation, are nonspecialized and are immortal so they enter the cycle repeatedly.
• They feature abnormal nuclei and an atypical number of chromosomes with extra copies of genes.
• They do not undergo apoptosis.
• Cancer cells form tumors and there is no contact inhibition.
• Undergo metastasis and angiogenesis, the formation of new blood vessels.

Cancer Cells vs. Normal Cells

• Cancer cells are nondifferentiated while normal cells are differentiated.
• Cancer cells feature abnormal nuclei, but normal cells have normal nuclei.
• Cancer cells do not undergo apoptosis, but normal cells do.
• Cancer cells do not exhibit contact inhibition, while normal cells do.
• Cancer cells are disorganized and multilayered, while normal cells are a single organized layer.
• Cancer cells undergo metastasis, but normal cells remain in their original tissue.

Progression of Cancer

• When tumors grow rapidly, blood vessels supplying nutrients and oxygen become insufficient
• New mutations arise, and one cell (brown) has the ability to start a tumor, which marks the primary tumor
• Cancer in situ refers to the tumor at its place of origin, where one cell (purple) mutates further.
• Cancer cells then invade lymphatic and blood vessels and travel throughout the body.
• New metastatic tumors can then be found some distance from the primary tumor.

The Origin of Cancer

• Normal growth and tissue maintenance depends on a balance between signals that promote and signals that inhibit cell division.
• Two types of genes can cause cancer in various ways when mutated.
• Proto-oncogenes/Oncogenes: Proto-oncogenes are normal genes that code for proteins which promote the cell cycle.
• If they are mutated they become an oncogene.
• Tumor suppressor genes: code for proteins which inhibit the cell cycle and promote apoptosis.
• If a tumor suppressor gene becomes inactive, it may promote cancer development.
• Poto-oncogenes are part of a stimulatory pathway, they promote progression through the cell cycle, include receptors and signaling molecules.
• 100 oncogenes can lead to tumors either by specifying an abnormal protein product or producing high levels of a normal products which leads to uncontrolled cell division.
• An example is BRCA1 mutations which can cause breast and ovarian cancer.
• Examples of mutations are the RB (Retinoblastoma) and p53 genes.
• RB gene is an inherited condition that results from a mutation in the RB gene, The p53 gene turns on the expression of other cell cycle inhibitory genes.
• Half of human cancers involve an abnormal or deleted p53 gene. Cancer can have viral, genetic and environmental causes.
• Chromosomes normally have special material at each end called telomeres.
• Telomeres get shorter after each cell division, and when they get very short, the cell will no longer divide.
• Telomerase is an enzyme that maintains the length of telomeres.
• Mutations in the telomerase gene can cause telomeres to continue to lengthen, which allows cancer cells to continuously divide.

Prokaryotic Cell Division

• The prokaryotic (bacteria and archaea) chromosome is a ring of DNA and a few associated proteins.
• Folded up in an area called the nucleoid and is replicated into two rings prior to cell division and the rings attach to the plasma membrane.
• Binary fission: is splitting in two, two replicate chromosomes are distributed to two daughter cells produces two daughter cells identical to original cell-asexual reproduction.
• Binary fission in prokaryotes and mitosis in cellular eukaryotes ensure that new cells are identical to parent cell.
• Mitosis in multicellular eukaryotes supports growth and repair of tissues.