12 The Cell Cycle Lecture Presentation by Cindy S. Malone, PhD, California State University Northridge

Please highlight all the terms in blue Please highlight all the terms in blue. When you are done with the notes, read chapter 12.

Introduction to Cell Division Cells arise through the division of preexisting cells. There are two types of cell division: meiosis and mitosis Both forms of cell division are accompanied by cytokinesis. The cytoplasm of the cell divides into two distinct daughter cells

Contrasting Mitosis and Meiosis Meiosis leads to: Production of gametes (eggs and sperm). Daughter cells have half the amount of genetic material as the parent cell. Mitosis leads to: The production of all other cell types referred to as somatic cells. Genetic material is copied and then divided equally. Daughter cells are genetically identical to the parent cell.

Functions of Mitosis Mitosis and cytokinesis are responsible for three key events in multicellular eukaryotes: Growth Wound repair Asexual reproduction

What Is a Chromosome? DNA encodes the cell’s genetic information. A gene is a section of DNA that encodes a specific RNA and therefore a specific protein. Chromosomes: Contain a single long double helix of deoxyribonucleic acid (DNA) and are wrapped around proteins.

Chromosomes Change before and during Mitosis The purpose of mitosis is to distribute chromosomes to daughter cells during cell division. Each chromosome is replicated before mitosis. Chromosomes condense from long, thin filaments into compact structures that can be moved around the cell. At the end of mitosis, one of the chromosome copies is distributed to each of two daughter cells.

Chromosome Replication Before mitosis, each chromosome is replicated. Each of the DNA copies in a replicated chromosome is called a chromatid. Chromatids: Are joined together along their entire length As well as at a specialized region of the chromosome called the centromere.

Chromosome Replication Chromatids from the same chromosome are referred to as sister chromatids. A replicated chromosome consists of two chromatids. It is still considered a single chromosome.

M Phase and Interphase Growing cells cycle between two phases: A dividing phase called the mitotic (M) phase A nondividing phase called interphase

Interphase: S Phase The cell cycle is: The orderly sequence of events That occurs from the formation of a eukaryotic cell Through the duplication of its chromosomes To the time it undergoes cell division

Interphase: S Phase Chromosome replication occurs only during interphase. It does not occur during M phase. The stage in which DNA replication occurs is called the synthesis (S) phase.

Interphase: Gap Phases Interphase also includes two gap phases, during which no DNA synthesis occurs G1 phase: Is the first gap Occurs before the S phase G2 phase: Is the second gap Occurs between S phase and mitosis

Interphase: Gap Phases During the gap phases: Organelles replicate Additional cytoplasm is made in preparation for cell division. It takes a cell about 24 hours to complete one cell cycle. G1 phase lasts 7–9 hours S phase lasts 6–8 hours G2 phase lasts 4–5 hours

The Cell Cycle There are a total of four phases in the cell cycle: M phase An interphase consisting of the G1, S, and G2 phases. Gap phases allow the cell to: Grow large enough Synthesize enough organelles to ensure the daughter cells. Be normal in size and function

(M) Mitosis Second gap First gap DNA synthesis (G1  S  G2) DIVISION Figure 12.3 DIVISION (M) Mitosis Second gap First gap Figure 12.3 The Cell Cycle Has Four Phases. DNA synthesis INTERPHASE (G1  S  G2) 16

Mitosis Overview Mitosis results in: The division of replicated chromosomes Formation of two daughter nuclei With identical chromosomes and genes Mitosis is usually accompanied by cytokinesis. Every species: Has a characteristic number of chromosomes Humans have 46 chromosomes

Chromosomes Change during the Cell Cycle Eukaryotic chromosomes consist of DNA associated with histone proteins. In eukaryotes, this DNA-protein material: Is called chromatin Is “relaxed” or uncondensed Forms long, threadlike strands

Chromosomes Change during the Cell Cycle After replication during S phase, each chromosome consists of: Two genetically identical sister chromatids Attached at the centromere At the start of mitosis, the replicated chromosomes condense.

Events in Mitosis During mitosis: The two sister chromatids separate to form independent chromosomes. One copy of each chromosome goes to each of the two daughter cells. Each daughter cell receives a copy of the genetic information that is contained in each chromosome.

Events in Mitosis Mitosis (M phase) is a continuous process with five subphases based on specific events: Prophase Prometaphase Metaphase Anaphase Telophase

Figure 12.4 INTERPHASE M PHASE Daughter cells G1 PHASE S PHASE G2 PHASE Parent cell Parent cell Parent cell Sister chromatids 4 unreplicated chromosomes (chromosomes are shown partially condensed to make them visible) 4 replicated chromosomes, each consisting of two sister chromatids At start of mitosis, replicated chromosomes condense. Figure 12.4 An Overview of the Cell Cycle. During mitosis, sister chromatids separate. Two daughter cells are formed by cytokinesis. 22

Prophase During prophase: The mitotic spindle: Chromosomes condense First become visible in the light microscope The mitotic spindle: Is made up of microtubules called spindle fibers Forms from a microtubule-organizing center Polar microtubules push the poles of the cell away from each other during mitosis. Kinetochore microtubules pull chromosomes to the poles of the cell during mitosis.

Prophase The microtubule-organizing center is a centrosome which contains a pair of centrioles.

Prometaphase During prometaphase: The nuclear envelope breaks down The nucleolus disappears Kinetochore microtubules from each mitotic spindle attach to one of the sister chromatids of each chromosome. Attachment occurs in the centromere region at the kinetochore.

Metaphase During metaphase: Formation of the mitotic spindle is completed Motor proteins on the kinetochore microtubules: Pull each chromosome in opposite directions Causing the chromosomes to line up in the middle of the cell. The imaginary plane formed by metaphase is called the metaphase plate.

Anaphase During anaphase: Centromeres split Sister chromatids are pulled by the spindle fibers toward opposite poles of the cell Replicated chromosomes split into two identical sets of unreplicated chromosomes. As soon as they are no longer attached at the centromere sister chromatids become daughter chromosomes.

Telophase During telophase: A new nuclear envelope begins to form around each set of chromosomes. The mitotic spindle disintegrates. The chromosomes begin to decondense. Mitosis is complete when two independent nuclei have formed.

Cytokinesis Cytokinesis typically occurs immediately after mitosis. During this process: The cytoplasm divides to form two daughter cells. Each daughter cell has its own nucleus and complete set of organelles.

4. Metaphase: Chromosomes complete migration to middle of cell. Figure 12.5-1 Sister chromatids separate; one chromosome copy goes to each daughter nucleus. Sister chromatids Kinetochore Centrioles Kinetochore microtubules Centrosomes Chromosomes Early spindle apparatus Polar microtubules Astral microtubules Figure 12.5-1 Mitosis and Cytokinesis. 1. Interphase: After chromosome replication, each chromosome is composed of two sister chromatids. 2. Prophase: Chromosomes condense, and spindle apparatus begins to form. 3. Prometaphase: Nuclear envelope breaks down. Microtubules contact kinetochores. 4. Metaphase: Chromosomes complete migration to middle of cell. 30

8. Cell division is complete: Two daughter cells form. Figure 12.5-2 Cytoplasm is divided. Figure 12.5-2 Mitosis and Cytokinesis. 5. Anaphase: Sister chromatids separate into daughter chromosomes and are pulled apart. 6. Telophase: The nuclear envelope re- forms, and chromosomes de-condense. 7. Cell division begins: Actin–myosin ring causes the plasma membrane to begin pinching in. 8. Cell division is complete: Two daughter cells form. 31

Different Cell Types Undergo Cytokinesis Differently Cytokinesis in plants occurs: As vesicles are transported from the Golgi apparatus to the middle of the dividing cell. These vesicles fuse to form a cell plate. Cytokinesis in animals, fungi, and slime molds occurs: When a ring of actin and myosin filaments contracts inside the cell membrane. Causing it to pinch inward in a cleavage furrow.

(a) Cytokinesis in plants (b) Cytokinesis in animals Figure 12.8 (a) Cytokinesis in plants (b) Cytokinesis in animals Microtubules direct vesicles to center of spindle where they fuse to divide the cell in two Actin–myosin interactions pinch the membrane in two Microtubule Cell plate Figure 12.8 The Mechanism of Cytokinesis Varies among Eukaryotes. Cleavage furrow 5 m 100 m 33

Different Cell Types Undergo Cytokinesis Differently Bacteria do not undergo cytokinesis: Instead, they divide via fission This is a process similar to animal cytokinesis

1. DNA is copied and protein filaments attach. Figure 12.9 New DNA Figure 12.9 Bacterial Cells Divide but Do Not Undergo Mitosis. Original DNA Replication enzymes 1. DNA is copied and protein filaments attach. 2. DNA copies are separated; ring of protein forms. 3. Ring of protein draws in membrane. 4. Fission complete. 35

Summary Table 12.1 Summary Table 12.1 Structures Involved in Mitosis 36

Cell-Cycle Checkpoints Many protein complexes are involved in regulating the cell cycle. There are three distinct cell-cycle checkpoints: During the four phases of the cell cycle Interactions among regulatory molecules at each checkpoint allow a cell to “decide” whether to proceed with division. If these regulatory molecules are defective the checkpoint may fail and cells may start dividing in an uncontrolled fashion.

1. chromosomes have attached to spindle apparatus Figure 12.12 G2 checkpoint M-phase checkpoints Pass checkpoint if: Pass checkpoints if: chromosomes have replicated successfully DNA is undamaged activated MPF is present 1. chromosomes have attached to spindle apparatus 2. chromosomes have properly segregated and MPF is absent Mitosis Second gap First gap Figure 12.12 The Four Cell-Cycle Checkpoints. DNA synthesis G1 checkpoint Pass checkpoint if: Mature cells do not pass this checkpoint (they enter G0 state) cell size is adequate nutrients are sufficient social signals are present DNA is undamaged 38

Cancer: Out-of-Control Cell Division Is a common, sometimes lethal disease Affects many humans Is a complex family of diseases caused by cells that: Grow in an uncontrolled fashion Invade nearby tissues Spread to other sites in the body

Cancer: Out-of-Control Cell Division Cancers vary widely in: Time of onset Growth rate Seriousness Cause Despite their differences, all cancers arise from cells in which cell-cycle checkpoints have failed.

Please highlight all the terms in blue Please highlight all the terms in blue. When you are done with the notes, read chapter 12.