How Cells Divide Chapter 9

2 Bacterial Cell Division Bacteria divide by binary fission. -the single, circular bacterial chromosome is replicated -replication begins at the origin of replication and proceeds bidirectionally -new chromosomes are partitioned to opposite ends of the cell -a septum forms to divide the cell into 2 cells

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4 Eukaryotic Chromosomes Eukaryotic chromosomes – -linear chromsomes -every species has a different number of chromosomes -composed of chromatin – a complex of DNA and proteins -heterochromatin – not expressed -euchromatin – expressed regions

5 Eukaryotic Chromosomes Chromosomes are very long and must be condensed to fit within the nucleus. -nucleosome – DNA wrapped around a core of 8 histone proteins -nucleosomes are spaced 200 nucleotides apart along the DNA -further coiling creates the 30-nm fiber or solenoid

6 Eukaryotic Chromosomes The solenoid is further compacted: -radial loops are held in place by scaffold proteins -scaffold of proteins is aided by a complex of proteins called condensin karyotype: the particular array of chromosomes of an organism

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9 Eukaryotic Chromosomes Chromosomes must be replicated before cell division. -Replicated chromsomes are connected to each other at their centromeres -cohesin – complex of proteins holding replicated chromosomes together -sister chromatids: 2 copies of the chromosome within the replicated chromosome

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In body cells, chromosomes occur as pairs. Each set of chromosomes is a homologous pair; each member is a homologous chromosome or homologue. One member of each homologous pair is inherited from the male parent, the other member from the female parent. look alike, have the same length and centromere position, and have a similar banding pattern when stained. A location on one homologue contains genes for the same trait that occurs at this locus on the other homologue, although the genes may code for different variations of that trait (called alleles). What are Homologous Chromosomes? (Mader 2007)

12 Eukaryotic Cell Cycle The eukaryotic cell cycle has 5 main phases: 1. G 1 (gap phase 1) 2. S (synthesis) 3. G 2 (gap phase 2) 4. M (mitosis) 5. C (cytokinesis) The length of a complete cell cycle varies greatly among cell types. interphase

13 Interphase Interphase is composed of: G 1 (gap phase 1) – time of cell growth S phase – synthesis of DNA (DNA replication) - 2 sister chromatids are produced G 2 (gap phase 2) – chromosomes condense

14 Interphase Following S phase, the sister chromatids appear to share a centromere. In fact, the centromere has been replicated but the 2 centromeres are held together by cohesin proteins. Proteins of the kinetochore are attached to the centromere. Microtubules attach to the kinetochore.

15 Chromatid Kinetochore microtubules Centromere region of chromosome Metaphase chromosome Cohesin proteins Kinetochore Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

16 Interphase During G 2 the chromosomes undergo condensation, becoming tightly coiled. Centrioles (microtubule-organizing centers) replicate and one centriole moves to each pole.

The cell cycle is controlled by both internal and external signals. A signal is a molecule that either stimulates or inhibits a metabolic event. Growth factors are external signals received at the plasma membrane. Cell Cycle Checkpoints There appear to be three checkpoints where the cell cycle either stops or continues onward, depending on the internal signals it receives. Researchers have identified a family of proteins called cyclins, internal signals that increase or decrease during the cell cycle. Cyclin must be present for the cell to move from the G 1 stage to the S stage, and from the G 2 stage to the M stage. The cell cycle stops at the G 2 stage if DNA has not finished replicating; stopping the cell cycle at this stage allows time for repair of possible damaged DNA. Also, the cycle stops if chromosomes are not distributed accurately to daughter cells. DNA damage also stops the cycle at the G 1 checkpoint by the protein p53; if the DNA is not repaired, p53 triggers apoptosis. Control of the Cell Cycle

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Apoptosis is programmed cell death and involves a sequence of cellular events involving: fragmenting of the nucleus, blistering of the plasma membrane, and engulfing of cell fragments by macrophages and/or neighboring cells. Apoptosis is caused by enzymes called caspases. Cells normally hold caspases in check with inhibitors. Caspases are released by internal or external signals. Apoptosis and cell division are balancing processes that maintain the normal level of somatic (body) cells. Cell death is a normal and necessary part of development: frogs, for example, must destroy tail tissue they used as tadpoles, and the human embryo must eliminate webbing found between fingers and toes. Death by apoptosis prevents a tumor from developing. Apoptosis

21 Mitosis Mitosis is divided into 5 phases: 1. prophase 2. prometaphase 3. metaphase 4. anaphase 5. telophase

22 Mitosis Prophase: -chromosomes continue to condense -centrioles move to each pole of the cell -spindle apparatus is assembled -nuclear envelope dissolves

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24 Mitosis Prometaphase: -chromosomes become attached to the spindle apparatus by their kinetochores -a second set of microtubules is formed from the poles to each kinetochore -microtubules begin to pull each chromosome toward the center of the cell

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26 Mitosis Metaphase: -microtubules pull the chromosomes to align them at the center of the cell -metaphase plate: imaginary plane through the center of the cell where the chromosomes align

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29 Mitosis Anaphase: -removal of cohesin proteins causes the centromeres to separate -microtubules pull sister chromatids toward the poles -in anaphase A the kinetochores are pulled apart -in anaphase B the poles move apart

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31 Mitosis Telophase: -spindle apparatus disassembles -nuclear envelope forms around each set of sister chromatids -chromosomes begin to uncoil -nucleolus reappears in each new nucleus

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33 Cytokinesis Cytokinesis – cleavage of the cell into equal halves -in animal cells – constriction of actin filaments produces a cleavage furrow -in plant cells – plasma membrane forms a cell plate between the nuclei -in fungi and some protists – mitosis occurs within the nucleus; division of the nucleus occurs with cytokinesis

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So What is the purpose of all of this? Mitosis is the way cells (within tissues and organisms) grow and repair Growth Repair 36

Many mammalian organs contain stem cells (or adult stem cells), which retain the ability to divide. Red bone marrow stem cells repeatedly divide to produce the various types of blood cells. Therapeutic cloning to produce human tissues can begin with either adult stem cells or embryonic stem cells. Embryonic stem cells can be used for reproductive cloning, the production of a new individual. Stem Cells

A neoplasm is an abnormal growth of cells. A benign neoplasm is not cancerous; a malignant neoplasm is cancerous. Cancer is a cellular growth disorder that results from the mutation of genes that regulate the cell cycle; i.e., cancer results from the loss of control and a disruption of the cell cycle. Carcinogenesis, the development of cancer is gradual — it may take decades before a cell has the characteristics of a cancer cell. The Cell Cycle and Cancer

Characteristics of Cancer Cells Cancer cells lack differentiation. Cancer cells have abnormal nuclei. Cancer cells form tumors. Cancer cells undergo metastasis and angiogenesis. The Cell Cycle and Cancer

Unlike normal cells that differentiate into muscle or nerves cells, cancer cells have an abnormal form and are nonspecialized. Normal cells enter the cell cycle only about 50 times; cancer cells are immortal in that they can enter the cell cycle repeatedly. Cancer cells lack differentiation

The nuclei may be enlarged and may have an abnormal number of chromosomes. The chromosomes have mutated; some chromosomes may be duplicated or deleted. Gene amplification, extra copies of genes, is more frequent in cancerous cells. Whereas ordinary cells with DNA damage undergo apoptosis, cancer cells do not. Cancer cells have abnormal nuclei

Normal cells are anchored and stop dividing when in contact with other cells; i.e., they exhibit contact inhibition. Cancer cells invade and destroy normal tissue and their growth is not inhibited. Cancer cells pile on top of each other to form a tumor. Cancer cells form tumors

A benign tumor is encapsulated and does not invade adjacent tissue. Cancer in situ is a tumor in its place of origin but is not encapsulated — it will invade surrounding tissues. Many types of cancer can undergo metastasis, in which new tumors form which are distant from the primary tumor. Angiogenesis, the formation of new blood vessels, is required to bring nutrients and oxygen to the tumor. A cancer patient ’ s prognosis depends on whether the tumor has invaded surrounding tissue, whether there is lymph node involvement, and whether there are metastatic tumors elsewhere in the body. Cancer cells undergo metastasis and angiogenesis

A DNA repair system corrects mutations during replication; mutations in genes encoding the various repair enzymes can cause cancer. Proto-oncogenes specify proteins that stimulate the cell cycle while tumor-suppressor genes specify proteins that inhibit the cell cycle; mutations of either of these genes can cause cancer. DNA segments called telomeres form the ends of chromosomes and shorten with each replication, eventually signaling the cell to end division; cancer cells produce telomerase that keeps telomeres at a constant length and thus the cells to continue dividing. Origin of Cancer

Proto-oncogenes are at the end of a stimulatory pathway from the plasma membrane to the nucleus; a growth factor binding at the plasma membrane can result in turning on an oncogene. oncogenes (cancer-causing genes). Tumor-suppressor genes are at the end of an inhibitory pathway; a growth-inhibitory factor can result in turning on a tumor suppressor gene that inhibits the cell cycle. The balance between stimulatory and inhibitory signals determines whether proto-oncogenes or tumor-suppressor genes are active, and therefore whether or not cell division occurs. Regulation of the Cell Cycle

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