Cell Cycle Regulation and Cancer Lecture #15 Honors Biology Ms. Day

Another Type of Cell Division: Binary Fission Prokaryotes (bacteria) Reproduce by a type of cell division called binary fission No nucleus  no karyokinesis!!

The bacterial chromosome replicates In binary fission, The bacterial chromosome replicates The two daughter chromosomes move apart Origin of replication E. coli cell Bacterial Chromosome Cell wall Plasma Membrane Two copies of origin Origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. 1 Replication continues. One copy of the origin is now at each end of the cell. 2 Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. 3 Figure 12.11 Two daughter cells result. 4

Cell Cycle needs to be controlled (Regulated) The cell cycle has 3 checkpoints A place where stop and go signals can regulate (control) cycle Signals make sure things been completed completed correctly There are 3 checkpoints G1 checkpoint G2 Checkpoint M checkpoint

The Cell Cycle Control System Figure 12.14 Control system G2 checkpoint M checkpoint G1 checkpoint G1 S G2 M

Checkpoint = give “go” or “stop” signals G1 checkpoint G1 G0 If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in cell cycle. If a cell does not receive a go-ahead signal at the G1checkpoint, cell exits the cell cycle and goes into G0, a nondividing state. Figure 12.15 A, B

Chromosomes are lined up in the middle properly of replicated DNA of unreplicated (original) DNA http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__control_of_the_cell_cycle.html

What controls the checkpoints? Two types of proteins in cytoplasm Cyclins cyclin-dependent kinases (Cdks)

CYCLIN DEPENDENT KINASE (CDK) INACTIVE FORM CYCLIN DEPENDENT KINASE (CDK) CYCLIN + ACTIVE FORM CDK/CYCLIN COMPLEX

Active vs. Inactive?? What happens when cyclins and cdks are in the ACTIVE form? Cells can pass through the cell cycle to the NEXT phase    What happens when cyclins and cdks are in the INACTIVE form? Cells can NOT pass through the cell cycle to the NEXT phase 

cyclin degrades & breaks apart cyclin degrades & breaks apart

What degrades (breaks down) cyclins? Proteolytic enzymes (proteins) Break down/degrade cyclins  cause them to fluctuate in [ ] “PROTEO” means protein “LYTIC” means break or lyse REMEMBER: Cyclin concentration fluctuates (changes) Cdk concentration stays the SAME

Programmed Cell Death (Apoptosis) If cell doesn’t “pass” checkpoint, it goes through apoptosis http://www.dnatube.com/video/1188/Apoptosis-animation Cell signaling is involved in programmed cell death needed to maintain healthy tissues/ cell function 2 µm Figure 21.17 http://bio-alive.com/categories/apoptosis/apoptosis.htm

What other things control cell division? Both internal and external signals control the cell cycle/cell division… Internal signals CDK/Cyclins at checkpoints External signals Growth factors Density dependent inhibition Anchorage dependence

External (outside the cell) Influences on Cell Division Growth factors Stimulate other cells to divide In density-dependent inhibition Crowded cells stop dividing Most animal cells exhibit anchorage dependence Cells must be attached to a structure to divide Ex: protein of a tissue or another cell

Normal mammalian cells. Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). Normal mammalian cells. **The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer. (a) 25 µm Figure 12.18 A

Loss of Cell Cycle Controls in Cancer Cells Abnormal dividing cells form tumors TUMOR= mass or group of abnormal dividing cells

Abnormally Dividing Cells make Tumors Two Types of Tumors: Benign  “fine” Clump of cells remain at orginal spot Malignant  “mean” “cancer” Loose/destroy attachments to other cells  they can spread or move (called metastasize)!!!

Cancer cells = continue to divide w/out rules Do NOT follow the “rules” No checkpoints and no density-dependent inhibition or anchorage dependence Immortal cells (if enough nutrients) 25 µm Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells. Figure 12.18 B

Why do cells break the “rules”? Don’t need growth factors  maybe they make their own growth factors Mutations in GENES that make proteins involved in control systems!!!

Cancer cells are “hungry”… Angiogenesis Making of blood vessels towards tumor Without blood and the nutrients it carries, a tumor would be unable to continue growing.

Cancer Treatment Radiation  destroys DNA in cancer cells (these cells have lost ability to repair damage) Chemotherapeutic drugs interfere with specific steps in cell cycle Also effects normal cells 

Figure 12.19 Tumor Lymph vessel Blood vessel Glandular tissue Cancer cell Blood vessel Lymph vessel Metastatic Tumor Cancer cells invade neighboring tissue. 2 Cancer cells spread through lymph and blood vessels to other parts of the body. 3 A tumor grows from a single cancer cell. 1 A small percentage of cancer cells may survive and establish a new tumor in another part of the body. 4 Figure 12.19

Movies for Review... Angiogenesis Cancer Movie http://www.cancerquest.org/index.cfm?page=3102&lang=english Angiogenesis http://www.hhmi.org/biointeractive/angiogenesis