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Chapter 16 Notes.docx

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Robert Boulianne

Chapter 16 – Cell Cycle Regulation and Cancer Cancer is a Genetic Disease • Single nucleotide substitutions to large scale rearrangements of the genome are associated with cancer. • Unlike other diseases, cancer is attributed to mutations that arise predominantly in somatic cells. – Rarely the result of a single mutation, rather an accumulation of mutations (sometimes 6-10)  Cancer is abnormal cell growth (benign tumor)  Abnormal restraints that keep cells from spreading and invading other parts of the body (metastasis).  Malignant tumor Malignant tumor o Billions of cells o Originated from one common ancestral cell  Important for its causes, diagnosis and prognosis.  Burkitt’s Lymphoma o Reciprocal translocations between chromosome 8 (breakpoint near c-myc gene) and chromosomes 2,14 or 22 near the immunoglobulin genes.  In every patient, all the lymphoma cells have the same breakpoints.  Each patient will have their own unique breakpoint.  The genetic basis for cancer is usually the accumulation of several mutations. Defects in Genome Stability and DNA Repair • Cancer cells show higher rates of mutation, chromosomal abnormalities and genomic instability – Mutator phenotype • Chronic Myelogenous Leukemia (CML) – Philadelphia chromosome – C-ABL gene fused to BCR gene • BCR-ABL fusion product is an abnormal signal transduction molecule stimulating cell proliferation in absence of growth signals. DNA Repair Defects • Xeroderma pigmentosum – Defective in nucleotide excision repair – Sensitive to UV light – Often develop skin cancer • Hereditary Nonpolyposis Colorectal Cancer (HNPCC) – Defect in DNA mismatch repair – Increased risk of developing colon, ovary, uterine and kidney cancers Cell Cycle Regulation • In addition to regulation at the checkpoints, cells control progression through cycle with: – Cyclins and CDKs (cyclin-dependent kinases) • The cell synthesizes and destroys cyclins in a precise pattern during cell cycle. • Cyclins bind to their specific CDK which activates the CDK/cyclin complex – Selectively phosphorylates and activates other proteins to bring about advance in cell cycle. Apoptosis • If DNA damage can’t be repaired, then the cell will activate programmed cell death (apoptosis). • Genetically controlled event leading to cell suicide – Nuclear DNA becomes fragmented – Internal cellular structures disrupted – Cell dissolves into small spherical bodies. • Carried out by caspases (proteases) M
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