Cell Cycle

Cell Cycle

• Gap 1 (Gsmall1)

• Synthesis (S) (copy the dna)

• Gap 2 (Gsmall2)

• Mitosis (M) (separate genetic material into two new nuclei)

• Cytokinesis (C) (cell moves to split)

Some cells continuously progress through the cell cycle whereas others delay the process after Gsmall1 or Gsmall2 indefinitely until cell division is required. The phases of the cell cycle are regulated by proteins called cyclins and enzyme kinases (CDKs).

Control of the Cell Cycle

The cell cycle is regulated by interaction of cyclins and cyclin-dependent kinases (CDKs)

Kinases (CDKs):

Enzymes that phosphorylate proteins (transfer a phosphate group [PO4 3- ) from ATP to a protein), activating the protein. CDKs activate specific cyclins, allowing the cell to initiate specific phases of the cell cycle. Specific CDKs activate specific cyclins (ex S-CDK activates S-cyclin; M-CDK activates M-cyclin). CDK concentrations remain relatively constant throughout cell cycle

Cyclins

Regulatory proteins where concentrations fluctuate throughout the cell cycle. Cyclins bind to and activate CDKs, initiating specific phases of cell cycle

Phases of the Cell Cycle

The process through which cell replicates. The cell cycle consists of Interphase and the Mitotic Phase.

Interphase

The longest portion of the cell cycle, during which the cell performs its normal functions while preparing for cell division. Interphase consists of three stages.

Gap 1 (Growth 1/ Gsmall1):

Longest stage of both interphase and the cell cycles. (some cells 5 min some years depends on what the cell is and its function). During this stage, the cell increases in size and some organelles replicate.  S-cyclin accumulates until it reaches a critical concentration

Mitosis

This is the distribution of chromosomes into two new nuclei. The copied DNA has condensed into identical chromosomes which attach forming sister chromatids. Spindle fibers will attach to the sister chromatids and pull them apart (to opposite poles/ends of the cell) into identical chromosomes. These chromosomes will unravel into chromatin within newly formed nuclei. Plants and animal cell mitosis are very similar processes, except that plants don’t use centrioles. This is a four phase process: prophase, metaphase, anaphase and telophase.

Mitotic Phase

Second phase of cell cycle, it included mitosis and cytokinesis.

Prophase

replicated DNA (chromatin) condenses into chromosomes. Centrioles (formed during G₂) migrate to opposite poles of the cell and form spindle fibers. The nuclear envelope begins to disintegrate.

Metaphase

During early metaphase (prometaphase), the identical chromosomes attach to each other (using centromere) forming sister chromatids. Sister chromatids align along the equator (metaphase plate) of the cell and spindle fibers attached to the sister chromatids at the centromere.

Anaphase

The shortest phase of mitosis. Spindle fibers contract, separating the sister chromatids as the centromeres split. The resulting separated chromosomes (identical) are pulled toward opposite poles of the cell.

Telophase

Chromosomes reach opposite poles of the cell. Spindle fibers disassemble. A new nuclear envelopes form around each set of chromosomes. The chromosomes uncoil, returning to the chromatin state.

Cytokinesis

Literally means “cell movement”. Cytokinesis is the physical division of the cytoplasm and plasma membrane, producing two daughter cells with identical DNA. This process differs slightly between plant and animal cells.

Animal Cell Cytokinesis

After telophase a contractile belt of microfilaments (metaphase plate) forms at the cell equator. The belt contracts (called furrowing) that pinches the cell into two daughter cells.

Plant Cell Cytokinesis

Because plant cells possess rigid cell walls which prevent furrowing. Golgi apparatus produces vesicles that migrate to the midpoint between the daughter nuclei. These vesicles fuse to form a cell plate. The membranes of the vesicles become the plasma membranes of the daughter cells. Materials released from the vesicles initiate construction of the new cell walls.

Factors That Influence Cell Division

Anchor Dependence and Density-Dependent Inhibition

Anchorage Dependence

Most animal cells must be attached (anchored) to another before they can divide

Density-Dependent Inhibition

Cells stop dividing when they become crowded and come into contact with neighboring cells. If cells are removed or die, neighboring cells resume dividing until the missing cells have been replaced and normal cell contact is restored.

Stem Cells

Undifferentiated cells capable of dividing and developing into a variety of specialized cell types.

Embryonic Stem Cells

Undifferentiated cells found in embryos during the first 13-14 days after fertilization. At this stage, these cells have the potential to develop into any cell type within the body. After approx 13-14 days, the cells begin to differentiate, forming the three germ layers of the embryo.

Pluripotent

Stem cells capable of differentiating into any cell type in the body. Embryonic stem cells are examples of Pluripotent cells.

Induced Pluripotent Stem Cell (iPS Cells)

Somatic cells  (usually skin or blood cells) that have been genetically reprogrammed to behave like embryonic stem cells. Used extensively in biomedical research and for therapeutic purposes.

Adult Stem Cells

Adults possess several different types of stem cells. Each type can differentiate into a limited variety of related cell types, these variations are somewhat similar. Adult stem cells are referred to as multipotent stem cells.

Cancer

A genetic disease (but usually not hereditary) that results in uncontrolled cell growth, due to failure of normal cell cycle regulation.This uncontrolled growth forms a malignant neoplasm (tumor). The failure of cell cycle regulation is often associated with mutations in the p53 gene. The p53 gene codes for a protein that checks for DNA mutations at the G₁/S checkpoint. Under normal circumstances, if DNA damage is detected, the p53 protein halts the cell cycle and repairs the damaged DNA before allowing cell cycle to resume. Because p53 prevents the development of most mutated cells, it is referred to as a tumor suppressor gene. Other genes involved in regulating the cell cycle may also mutate, leading to cancer. These mutations generally occur after birth, either as replication errors or as the result of exposure to carcinogens. Because these mutations usually occur in somatic cells and are not passed from one generation to the next, cancer is generally not considered a hereditary disease, even though it results from mutations in DNA. Cancer is not a single disease but rather a group of diseases that are classified according to the tissue or cell type from which they originate.

Genetic Basis of Cancer:

Cancer results from uncontrolled cell cycle, leading to uncontrolled cytokinesis and cell proliferation. Because cell division occurs so rapidly, cells divide before they have fully matured or differentiated. As a result, cancer cells are often immature, function poorly, and continue to divide uncontrollably. The underlying cause of this uncontrolled cell division is usually a mutation in one or more of the genes that code for proteins responsible for regulating the cell cycle. These mutations generally occur after birth and are not inherited from the parents.

Tumor Suppressing Genes

Every cell contains genes that code for protein responsible for inhibiting cell division. These proteins help prevent uncontrolled cell growth. Many tumor suppressor genes code for proteins that repair damaged DNA (ex p53). When these genes become mutated, the likelihood of uncontrolled cell division increases, as does the probability that additional cancer-causing mutations will accumulate.

Oncogene

Mutated forms of genes that code for proteins regulating the cell cycle. Because these genes are mutated, they continually produce malfunctioning proteins that fail to properly regulate (restrain) cell division

Proto-Oncogene

Normal genes that promote and regulate the cell cycle. When proto-oncogenes mutate, they become oncogenes.

Causes of Cancer

Cancer results from genetic mutations (changes in DNA) that occur after birth. Therefore, cancer is generally not considered hereditary. Cancer develops when tumor suppressor genes or proto-oncogenes become mutated. The cell cycle then progresses unregulated, producing cancerous cells that are immature, abnormal, and contain mutated DNA. Cancer cells also lose anchorage dependence and density-dependent inhibition. Allowing them to divide rapidly and uncontrollably. These mutations generally arise through one of three major mechanisms: carcinogens, viruses, replicative mutations

Carcinogens

Cancer-causing agents that cause mutations in cellular DNA, particularly in tumor suppressor genes and proto-oncogenes. Cardinogens may directly damage DNA or kill cells that must later be replaced. Increased cell division during tissue repair increases the probability of replication errors (due to replicative mutations). Two major categories of carcinogens are: chemical carcinogens and radiation.

Viruses

Some viruses insert their genetic material into the DNA of the cells they infect. VIral DNA may mutate proto-oncogenes or tumor suppressor genes.

Ex. -Epstein Barr Virus (infectious mononucleosis) has been associated with several cancers.

-Human Papillomaviruses (HPV) have been strongly associated with cervical cancers.

Replicative Mutations

Most genetic mutations (both beneficial and harmful) occur during the S phase of the cell cycle while DNA is being replicated. During DNA replication, mutations may occur in proto-oncogenes, converting them into oncogenes, or in tumor suppressor genes, reducing or eliminating their normal function.

Neoplasm

(NEW GROWTH) An abnormal new growth of tissue resulting from accelerated cell division.Neoplasms develop, in part, because cancer cells fail to exhibit density-dependent inhibition and anchorage dependence. These growths are commonly called tumors and are classified as either benign or malignant.

Benign

A mass of cells whose genetic composition does not differ significantly from that of the surrounding tissue (DNA is generally not mutated in ways that promote invasion) Cell division occurs at a rate only slightly greater than that of normal tissue. Benign tumors are enclosed within a connective tissue capsule. Cells remain localized and do not invade surrounding tissues or spread to distance sites. Because cell division is only moderately accelerated, these tumors generally grow slowly.

Malignant

Neoplasms whose DNA has accumulated mutated, causing the cells to differ genetically and structurally from the surrounding tissue. Cells resemble immature (undifferentiated) cells. Cell division (growth) is greatly accelerated, producing rapid, uncontrolled, and disorganized growth. Malignant tumors break through the surrounding connective tissue capsule allowing malignant cells to spread throughout the body. Malignancies are classified according to the tissue or cell type from which they originate.

Metastasis

The spread of cancer from its original location to other tissues through the lymphatic system or bloodstream. Death from cancer most commonly results from metastasis, when secondary tumors develop in distance tissues and interfere with normal organ function. If metastatic growth is not controlled, normal physiological functions will be compromised until life can no longer be sustained.

Process of Metastasis

As malignant tumors break through their connective tissue capsule, cancer cells escape from the primary tumor. These cells enter body cavities, the bloodstream, or the lymphatic system. These “escaped” cells are transported to distant tissues, where they implant and divide to form secondary neoplasm (secondary tumors). Most cancer-related deaths result from these secondary tumors rather than from the primary tumor itself.