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How long does the cell cycle last? Depends on the cell stem cells, embryonic cells- a few hours Some cells divide very slowly Some cells divide when induced liver lymphocytes Some cells don’t divide nerve cells What controls the cell cycle? Cell division Interphase : Cell growth (G1 and G2) S Phase : DNA is replicated M phase : Division of nucleus (mitosis) Cytokinesis: Division of cytoplasm Apoptosis: Programmed cell death Cells divide only a certain number of times and then die (Hayflick limit) Role of telomeres? Control of cell cycle special proteins and enzymes that act as switches G1 checkpoint- stop, pause or go into S phase some cells stop permanently G2 checkpoint- will cell divide? M checkpoint- formation of new cells Early 1970s: Experiments with Cell Fusion M phase drives G1 cell into mitosis, even though S phase has not occurred S + G1: G1 cell starts S phase S phase + G2: G2 will not undergo DNA synthesis G1 checkpoint Varies the most among cell types First of several checkpoints is seen What determines whether a cell will grow? Single-celled organisms grow if enough nutrients are present Multicellular organisms must grow in a controlled way: growth factors Mitogens stimulate cells to go into S phase How do growth factors work? Bind to tyrosine kinase receptors Activate Ras pathway (a small membrane G protein) Cascade of phosphorylation reactions, followed by transcription Cell passes into S phase G2 checkpoint (between G2 and M) DNA synthesis must be complete and correct Cell may be arrested at this point This checkpoint tends to be more important in certain types of cells, e.g., fertilized frog eggs and certain strains of yeast Cyclin-dependent kinases (Cdk) First discovered in yeast Different kinds of cyclins; levels oscillate at different stages of cycle Control mechanisms availability of cyclins varies Cdk (cyclin dependent kinases) must be phosphorylated Cyclin and Cdk must be bound together to be active Initial cyclin-Cdk complex is inactive a series of phosphorylation and dephosphorylation steps make it active Complex is called MPF (mitosis-promoting factor) Present in both mitosis and meiosis Highly conserved MPF activates a complex that degrades cyclin Spindle assembly checkpoint Between metaphase and anaphase Cell cycle can be arrested if spindle fibers are not attached properly to chromatids Genes controlling G1 checkpoints 1. Rb prevents cell moving into S phase by binding to a transcription factor When Rb is phoshporylated it cannot bind so cell can move into S phase 2. p53 prevents damaged cells from dividing (by inhibiting Rb pathway) Abnormalities in both genes are associated with hereditary forms of cancer Regulation of Cell Growth Controls: contact inhibition- cells will grow to a certain density finite number of cell divisions “gatekeeper genes” proto-oncogenes- stimulate growth some make growth factors some respond to growth factors Types of proto-oncogenes Growth factors Receptors (G protein and tyrosine kinase) Kinases Transcription factors Cdk-kinases Mutant forms, oncogenes that promote cancer, have been identified in every category Tumor suppressors- inhibit cell growth Cancers occur • when cells grow out of control • invade and damage tissues • cells themselves may not function properly How does this happen? Mutations accumulate in DNA If mutations occur in control genes, they can’t regulate cell growth Some defects in particular genes are associated with specific cancers BRCA-1 tumor suppressor gene associated with some inherited breast cancers p53- tumor suppressor- associated with many colon, bladder, breast, brain, lung cancers (about half of all cancers!) Apoptosis – Cell Destruction Damaged cell undergoes apoptosis (programmed cell death) Genetically regulated- cell has genes that both promote and inhibit death How does programmed cell death differ from death by injury? Inheritance of “cancer gene”: Each cell has 2 copies of p53. If both become damaged, they lose control of cell growth If you inherit one “damaged” copy, you’re halfway there! Mutations occur over time- cancer is more common in older people Most cancer is NOT inherited; environmental damage causes most cancer What sorts of things cause this damage? Radiation Toxins Chemicals Our bodies have many processes that repair damaged DNA Avoid sun exposure Avoid smoking Eat moderately; consume fiber. Some foods may help prevent cancer? Early detection (especially important if you have a family history of cancer)