Cell Cycle/Cancer

Department of Biological and Environmental Sciences
Cell & Molecular Biology
Dr. David A. Johnson
Biol 405 4 Credits Spring 2017 MWF 11:45-12:50 AM PH 204

<<< The Cell Cycle: An Overview

The events of the cell cycle are intricately regulated in eukaryotes. When this regulation goes awry, one possible result is cancer.
The Cell Cycle: Dividing cells undergo the processes of of cell growth, DNA replication, mitosis, and cytokinesis. This cycle is the cell cycle and consists of G1, S, G2, and M. S (synthesis) is the phase during which DNA replication occurs. It is preceded by G1, during which cell growth is apparent. S is followed by G2 then by M (mitosis). Non-dividing cells exit G1 and enter the stage called G0 if the certain growth factors are not present. This is the restriction point (analogous to START in yeast).
The Regulation of the Cell Cycle and Cell Cycle Checkpoints: At various points in the cell cycle, the cell stops and checks to make sure everything is in order before proceeding. These are called checkpoints and there are 4 major ones in the cell cycle: The G1/S Checkpoint (a DNA-Damage Checkpoint): At this checkpoint near the end of G1, the cell cycle will halt if the DNA has damage that needs to be repaired. The S Checkpoint (a DNA-Damage Checkpoint): At this mid-S checkpoint also the cell cycle will halt if the DNA has damage that needs to be repaired. (Research news) The G2/M Checkpoint (a DNA-Damage Checkpoint): At this checkpoint near the end of G2, the cell cycle will halt if DNA replication is not complete or it DNA damage is detected. (Regulated by MPF, below) The M Checkpoint (Spindle-Assembly Checkpoint): At this checkpoint (also called the spindle assembly checkpoint) around anaphase, mitosis is halted unless the chromosomes have properly aligned. This checkpoint is why cells will not divide when a spindle inhibitor like colchicine is added.
MPF, Cyclin B, and Cdk1: an Example of the Mechanism of Cell Cycle Regulation: The mechanism of regulation of the entry into mitosis at the G2/M checkpoint involves the active form of the protein MPF (cyclin B/Cdk1 complex phosphorylated at one amino acid, dephosphorylated at two other amino acids). (MPF stands for "maturation promoting factor.") This is related to the continual synthesis of cyclin, its degradation, a kinase that phosphorylates Cdk1, and a phosphatase that dephosphorylates Cdk1. DNA damage activates a separate kinase that results in deactivation of MPF. (Cell cycle control video.) Examples of Cdk1/Cyclin B's Action: Condensins (protein complexes that are responsible for chromosome condensation during mitosis and meiosis) are activated by Cdk1/cyclin B phosphorylation. Also, the breakdown of the nuclear envelope that occurs at the outset of prophase (or prophase I). The membrane breakdown involves the phosphorylation of lamins by Cdk1/cyclin B, causing their depolymerization. (Other cyclins initiate other events: video at about 6:30.) *Other Genes/Factors:* A tumor suppressor gene on the short arm of chromosome 17 makes the p53 protein. When DNA is damaged, this protein causes other proteins to bind to Cdk thereby inactivating it, so the cell cycle halts. p53 is also involved in stimulating DNA repair, and, if the cell is damaged beyond repair, stimulating apoptosis (programmed cell death). A defective p53 gene will allow cells that have damaged DNA to continue to divide, thus possibly leading to cancer. People with only one functional copy of the p53 gene have a high chance of developing tumors, a disease known as Li-Fraumeni syndrome (http://en.wikipedia.org/wiki/Li-Fraumeni_syndrome).

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