Cell Cycle Pg J-59 (see handout)

Rudolf Virchow A German Physician 1855 : “Where a cell exists, there must have been a preexisting cell, just as the animal arises from an animal and the plant only from a plant.” “Omnis cellula e cellula”

Format of Cell Growth Cell Growth Increase in the number of cells Increase in the size of cells Volume – Surface Area Relationship Volume increases as the cube of the radius Surface area increases as the square of the radius Problems with transport – wastes out of cell and nutrients into cell

The Nucleus Controls Metabolic Functions Chromosomes (DNA) contain genetic information for all aspects of cell structures and functions Must produce EXACT copy of nucleus (chromosomes) for each new cell

Definitions Cell cycle : The life of a cell from its origin in the division of a parent cell until its own division into two Genome : The total DNA of a cell Chromosomes : Packages of DNA molecules Somatic Cells : All body cells except the reproductive cells (46) Gametes : Reproductive cells (23)

More Definitions Chromatin : DNA-Protein complex within the nucleus Sister Chromatids : Identical duplicated chromosomes Centromere : The centralized region joining two sister chromatids

Mitosis or Karyokinesis Duplication and division of nucleus and its contents (chromosomes) Need exact copies of cells with complete set of genetic information

Chromosome Duplication

A: Interphase Accounts for 90% of Cell Cycle Metabolically active – growth and synthesis Typical Eukaryotic appearance Chromosomes present but not visible Chromatin – long thin thread like appearance of the DNA + protein in an uncoiled nature Animal cells have 2 pairs of centrioles outside of the nuclear region Interphase : Divided into three sub-phases G 1, S, and G 2

A: Interphase G1 First “Gap” Cell is growing S Chromosomes duplicated G2 Second “Gap” Cell grows more in anticipation of cell division

Chromosomes of Interphase : DNA plus protein core Chromatin : thin thread like appearance DNA is metabolically active as cell functions and grows = G 1 Synthesis of new DNA = exact copies of each chromosome 46 chromosomes = G 1 92 chromosomes = S (synthesis of DNA) S = this cell is preparing to divide …….how do you know cell has completed S if chromatin isn’t visible? Weigh cell X ng vs. 2X ng

G 2 – Second Growth (Gap) This specific growth is directed towards cell division Different from G 1 Proteins for spindle fibers, etc

Progression of Chromosomes

Cell Cycle Regulation Checkpoint – stop and go-ahead signals can regulate the cycle Animal cells will typically stop at check points unless being overridden by go-ahead signals Three Major checkpoints : G 1, G 2, M phases G 1 Checkpoint –most important If the cell passes G 1 it will typically complete the cycle and divide G 0 phase – a Non-dividing state Most cells of the human body are in this state

Figure Mitotic Regulation

Cyclins and Cyclin – Dependent Kinases Kinases : enzymes that activate or inactivate other proteins by phosphorylation Not active unless attached to a cyclin Cyclin – a protein that cyclically fluctuates within the cell Kinases are called : cyclin-dependent kinases (CDKs) MFK – promotes mitosis by phosphorylating various proteins Maturation-promoting-factor Discovered first

Figure Molecular control of the cell cycle at the G 2 checkpoint

Figure The effect of a growth factor on cell division - Fibroblasts

Figure Density-dependent inhibition of cell division *Cells typically grow in a density dependent manner *Cells are anchorage dependent - they must attach to a container wall or ECM *This is the normal state *Cancer cells do not exhibit a density or anchorage dependence -they have escaped cell cycle controls!

Cancer Cells Escape cell cycle controls No anchorage or density dependence Can divide in culture infinitely Most cells divide times and die Cancer cells = “Immortal”

Cancer Cells A normal cell undergoes “transformation” If it survives the immune system it can proliferate into a tumor A mass of abnormal cells within a normal tissue Benign Cells remain at the original site Malignant Becomes invasive enough to effect other organs

Figure The growth and metastasis of a malignant breast tumor