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Our bodies consist of trillions of cells.
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These cells need to divide when our bodies grow,
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replenish the cells we've lost from injuries,
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or need to maintain cell populations, like that
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of the skin.
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The mitotic cell cycle is the process
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by which all eukaryotic cells replicate and divide
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to produce daughter cells for growth, repair,
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and development.
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Because the cell cycle is vital to our survival,
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our cells tightly regulate the process
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to prevent uncontrolled cell division or incorrect DNA
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replication, which can lead to diseases, like cancer.
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This video gives an overview of the steps
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within the cell cycle, and introduces
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some of the key proteins that help our bodies regulate
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cell division.
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We will use language that is defined in our cell cycle terms
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video.
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So we recommend that you watch that video,
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if you haven't already done so.
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How, exactly, does the cell cycle
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enable DNA replication and cell division to produce more cells?
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We divide the cell cycle into four main phases--
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G1, S, G2, and M. We group these phases
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into two more general phases--
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interphase, during which the cell
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prepares for cell division, and the mitotic phase,
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when cell division occurs.
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In experimental assays, populations of cells
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can be either synchronous or asynchronous.
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A synchronous population of cells
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contains cells that are all in the same phase of the cell
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cycle--
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for example, a cell culture with many cells
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that are all beginning mitosis simultaneously.
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Cells in an asynchronous population
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are spread throughout the cell cycle stages.
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For example, some cells will be in S phase,
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while others are in M phase and actively dividing.
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This video focuses on one phase of the human cell cycle
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at a time, paying specific attention
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to how much genetic material is in the cell at each point.
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Note that when cells are not dividing,
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they often enter a quiescent stage, called the G0 phase.
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These cells are performing their unique functions,
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but are not undergoing cell growth or division.
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Because these cells are not dividing,
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they will have 46 homologous chromosomes, or 2N chromosomes,
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no sister chromatids, and 2C DNA content,
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because the cell is diploid and no DNA
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replication has occurred.
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The G1, or Gap 1, phase involves cell growth and preparation
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for DNA replication, which will take place in S phase.
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This preparation includes checking
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for cells with DNA damage, making
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sure there are enough nutrients in the cell for cell division,
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and verifying that the cell is big enough to divide.
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During the G1 phase, the cell also
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prepares for initiation of DNA replication.
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Specifically, proteins identify origins of replication and load
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multi-protein complexes onto this DNA,
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for example, the DNA helicase.
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How many chromosomes are currently
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in the cell after G1 phase?
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Try to fill out this table.
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Right now, the diploid eukaryotic cell
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has 2N chromosomes, 46 in humans.
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The cell modified the DNA to prepare for DNA replication.
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But no replication has occurred and, therefore,
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the number of chromosomes and genetic material
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is still the same as in G0.
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That is, sister chromatids have not formed
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and the cell has 2C DNA content because the cell is diploid
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and no DNA replication has occurred.
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At the end of G1, there's a point of no return,
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often called the restriction point,
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where the cell commits to completing the rest of the cell
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cycle and transitions into the S phase.
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DNA replication occurs in the S, or synthesis, phase.
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The cell now activates the DNA helicases that the cell loaded
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onto DNA in G1 phase.
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This process separates the double-stranded DNA
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into single-stranded DNA to provide the templates
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for DNA replication.
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The sites of helicase action are junctions
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between double-stranded and single-stranded DNA,
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which form replication forks.
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Many other proteins assemble at these sites, like DNA
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polymerase, primase, and others, to replicate the DNA strands.
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The cell does not load helicases during S phase,
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to ensure that the DNA is replicated once and only once.
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DNA replication results in duplicated chromosomes,
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sister chromatids that are held together
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by proteins that promote sister chromatid cohesion.
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Remember that sister chromatids are identical copies
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of a single chromosome.
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Now how many chromosomes are currently in the cell,
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after S phase?
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And how many copies of the DNA?
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Try to fill out this table.
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Right now, the cell is still 2N, with 46
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unique homologous chromosomes.
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The DNA replication duplicates each
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of these individual chromosomes to form 46 pairs
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of identical sister chromatids.
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And there's 4C DNA content now, because DNA replication has
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occurred in this diploid cell.
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G2 phase is a gap phase that allows the cell
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to prepare for N phase, during which the cell will divide
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in two.
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This preparation mainly includes verifying
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that S phase completed correctly and that the chromosomes were
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completely and accurately replicated,
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with no need for DNA repair or further DNA replication.
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Now how many chromosomes are currently in the cell after G2,
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and how many copies of the DNA?
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Try to fill out this table.
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Right now, the cell is still in the exact same state
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as it was at the end of S phase.
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There are 2N, or 46 unique homologous chromosomes,
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that have been duplicated to form
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46 pairs of sister chromatids.
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Because DNA replication occurred in S phase,
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there's still 4C DNA contents in the cell.
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Chromosome segregation occurs during M phase, or mitosis.
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We divide mitosis into subphases--
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prophase, metaphase, anaphase, and telophase, directly
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followed by cytokinesis, or cell division.
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Prophase is when the pairs of sister chromatids
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condense to form the familiar chromosome shapes we
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see in textbook illustrations.
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The nuclear envelope in the cell also breaks down.
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To simplify these animations, we only
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show 3 of the 46 pairs of sister chromatids in a human cell.
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But keep in mind that the remaining pairs are still
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there.
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Metaphase is when the mitotic spindle forms.
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This structure is a molecular machine
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that separates the sister chromatids,
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ensuring that each daughter cell gets
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one copy of each chromosome.
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During metaphase, the filaments--
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microtubules from the poles of the mitotic spindle,
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centrosomes--
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attach to the pairs of sister chromatids
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on both sides of the region called the centromere.
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The tension from mitotic filaments,
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pulling the pairs of sister chromatids
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toward the opposite poles of the mitotic spindle,
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aligns the chromosomes in the center of the cell.
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This is called the metaphase plate.
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Anaphase is when the sister chromatids separate and are
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pulled to opposite sides of the cell by the mitotic spindle.
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Now each side of the cell, which will
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become one of the two daughter cells,
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has a complete set of 46 chromosomes.
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During telophase, the nuclear envelope
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begins to re-form around each group
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of segregated chromosomes.
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These chromosomes also begin to decondense once more.
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Cytokinesis is not technically a phase of mitosis,
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but follows immediately afterward.
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During cytokinesis, the plasma membrane of the mother cell
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fuses in a way that physically separates
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the cytoplasm of the mother cell to form
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two daughter cells, each with their own nucleus
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and chromosomes.
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Now how many chromosomes are currently
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in each daughter cell?
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And how many copies of the DNA?
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Try to fill out this table.
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Each daughter cell is 2N, with 46
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unique homologous chromosomes.
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The pairs of sister chromatids have separated and are now
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just considered to be individual chromosomes in each
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of the daughter cells.
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Each new cell now only has two 2C DNA content,
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like all diploid cells.
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Now the cell cycle is ready to start all over again,
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with each of these daughter cells,
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or the cells can stop growing and arrest in the G0 phase.
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The cell cycle involves many steps, all of which
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are equally important to ensure that the replication
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of genetic material and cell division goes correctly.
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Now that you're familiar with the phases of the cell cycle,
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let's talk about what regulates these phases.
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How does the cell know what phase it's in,
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and how does it know that it's safe to proceed
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to the next phase?
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The cell cycle is regulated by a class of proteins called
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cyclins which, in turn, activate cyclin-dependent kinases,
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or CDKs.
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The name cyclin reflects their property
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of fluctuating in abundance in specific ways
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during the cell cycle, as you can see in this diagram.
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The abundance of cyclin and cyclin CDK activity
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divide the cell cycle into the distinct phases
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we described before--
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G1, S, G2, and M.
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In addition, there are checkpoints during the cell
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cycle that check the work of the cell
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and ensure that one phase is complete
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before the next is started.
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For example, there's a checkpoint
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that prevents cells from entering mitosis until DNA
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replication is complete.
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This prevents catastrophic errors,
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such as segregating incompletely replicated chromosomes, which
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would lead to chromosome breaks and DNA damage,
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which could in turn lead to diseases like cancer.
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The cell cycle is essential for our growth and survival.
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The cell cycle can appear complicated
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because it integrates many smaller, equally complicated
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cellular processes, such as DNA replication and mitosis.
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Now that you've finished this video,
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can you explain the four different stages
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of the cell cycle, and what occurs in each step?
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And do you have an idea of what role cyclin and CDKs play
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in regulating the cell cycle, and why
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they are important to our overall health?
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Thanks for watching.
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