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Mitosis & Cell Cycle Why? When? How? Cells must reproduce else they die. The "life of a cell" is termed the cell cycle. The cell cycle has distinct phases, which are called G1, S, G2, and M. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase. • During this time organelles are reproducing, protein synthesis is occurring for growth and differentiation. • Because, transcription is occurring, the DNA is uncoiled. • This phase is the most variable, ranging from almost nothing to years. The S or synthesis phase is the second phase of the cell cycle. • DNA uncoils • DNA replication occurs • Additional organelle replication occurs • This phase ensures that each emerging daughter cell will have the same genetic content as the mother cell. Chromatin chromosome sister chromatids DNA polymerase must always attach the complementary nucleotide to a 3 end of the deoxyribose sugar molecule. So, in the very beginning a small RNA primer must be laid down in order to start the process of DNA replication. Primase is the enzyme responsible for this. Since DNA is a double helix, there will be tension in the DNA strand that causes it to tangle as it is unwound by the helicase. The enzymes topoisomerase I and II are responsible for relieving that stress by clipping one or two strands of the DNA. When DNA replicates each strand of the original DNA molecule is used as a template for the synthesis of a second, complementary strand. Which of the following sketches most accurately illustrates the synthesis of a new DNA strand at the replication fork? ’ a. c. d. b. The G2 or Gap 2 phase occupies the time from the end of S until the onset of mitosis. •During this time, the cell prepares for mitosis by making and organizing necessary proteins such as the tubulin needed to construct microtubules which used to make spindle fibers. If we estimate that 90% of the cell cycle is spent in interphase, do these results support this? Yes, this data supports this estimation To get the percentages, divide the number of cells in each stage by the total number of cells, then multiply by 100. 2250/2500 = 0.9 0.9 x 100 = 90% If this cell goes through the entire cell cycle in 24 hours, approximately how long are the cells in anaphase. Round your answer to a whole number in minutes. 30 minutes 50/2500 = 0.02 x 100 = 2% 24 hours x 60 minutes = 1440 minutes 2% (or 0.02) x 1440 = 28.8 round to 30 minutes Mitosis is division of the nucleus. During interphase the cell has increased in size, has replicated organelles, proteins have been synthesized, and the DNA has been replicated. Interphase takes About 90% of the time that a cell spends in the cell cycle. Mitosis consists of• Prophase • Metaphase • Anaphase • Telophase Cytokinesis (division of the cytoplasm) is usually happening At the same time as telophase Interphase ProphasePrometaphase Chromatin condenses and becomes visible as chromosomes/chromatids Centrioles move to opposite poles of the cell (in animal cells) Nucleolus disappears Nuclear envelope breaks down Microtubules attach at kinetochores Metaphase Spindle fibers align chromosomes along the middle of the cell Anaphase Sister chromatids separate to become individual chromosomes pulled apart by motor proteins walking along microtubules Telophase Chromosomes arrive at opposite poles Nucleoli reform Chromosomes uncoil Spindle fibers disperse Cytokinesis begins The Amount of DNA Varies During the Cell Cycle This graph represents the amount of DNA found in the cell during the cell cycle. Which choice is a correct explanation? A. DNA replication occurs during G2 B. During G1 the cell is dormant, there is no cellular activity C. S stands for size; the cytosol is doubling D. During prophase and metaphase the chromosomes exist as sister chromatids 22 What is the goal of cell division? Regulation of Cell Division Do all cells have the same cell cycle? Cell Cycle Control “Stop and Go” chemical signals at specific points 3 Major Checkpoints G1- Can DNA synthesis begin? G2-Has DNA synthesis been completed correctly? Commitment to mitosis M phase Check the spindle. Can sister chromatids separate correctly? G1 Checkpoint Most critical, the primary decision point If cell receives “go” Signal it divides If it doesn’t receive “go” signal, cell switches Into Go phase “Go” signals can be proteins or growth factors that promote cell growth & division The primary mechanism of control is phosphorylation by kinase enzymes Cyclins vs. Kinases • Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes. • A kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. 27 Cyclins vs. Kinases • Certain cyclins are made at certain times during the cell cycle, and their concentration will rise and fall. Cyclins are also destroyed after they are no longer needed by the cell. • CDKs are not destroyed as they are only activated or deactivated. 28 According to the graph, high concentrations of which cyclin(s) must be present for DNA replication? a. A and B b. D only c. D and E d. E only Proto-oncogenes can change into oncogenes that cause cancer. Which of the following best explains the presence of these potential time bombs in eukaryotic cells? a. b. c. d. Proto-oncogenes first arose from viral infections Proto-oncogenes normally help regulate cell division Proto-oncogenes are genetic “junk” Cells produce proto-oncogenes as they age Proto-oncogenes- normal cellular genes that code for Proteins that stimulate normal cell division and growth are altered Oncogene- proto-oncogene becomes so mutated that it Becomes a cancer causing gene p53 gene •“Guardian of the Genome” The “anti-cancer gene” After DNA damage is detected, p53 initiates: oDNA repair ogrowth arrest oapoptosis •Almost all cancers have mutations in p53. The p53 gene is a tumor suppressor gene (its activity stops the formation of tumors). If a person inherits only one functional copy of the p53 gene they are predisposed To cancer and usually develop several independent tumors in a variety of tissues in early adulthood. This condition is rate, and is known as Li-Fraumeni syndrome. However, mutations in p53 are found in most tumors, and so contribute to the complex molecular events leading to tumor formation. The p53 gene has been mapped to chromosome 17. In the cell, p53 binds to DNA, which stimulates another gene to produce a protein called p21 that interacts with a cell division stimulating protein (cdk2). When p21 is attached to cdk2, the cell cannot pass to the next stage of cell division. Mutant p53 can’t bind to DNA and the p21 protein is not available to act as the “stop signal” for cell division. Cells divide uncontrollably and form tumors. The BRCA1 gene belongs to a class of genes known as tumor suppressor genes. Like many other tumor suppressors, the protein produced from the BRCA1 gene helps prevent cells from growing and dividing too rapidly or in an uncontrolled way Research suggests that the BRCA1 protein also regulates the activity of other genes and plays a critical role in embryonic development. To carry out these functions, the BRCA1 protein interacts with many other proteins, including other tumor suppressors and proteins that regulate cell division.