11 The Cell Cycle and Cell Division. 11 The Cell Cycle and Cell Division 11.1 How Do Prokaryotic and...

11The Cell Cycle and

Cell Division

11 The Cell Cycle and Cell Division

11.1 How Do Prokaryotic and Eukaryotic Cells Divide?

11.2 How Is Eukaryotic Cell Division Controlled?

11.3 What Happens During Mitosis?

11.4 What Role Does Cell Division Play in a Sexual Life Cycle?

11.5 What Happens during Meiosis?

11.6 In a Living Organism, How Do Cells Die?

11.7 How Does Unregulated Cell Division Lead to Cancer?

Opening Question:

What makes HeLa cells reproduce so well in the laboratory?

The first human cells to be grown in the laboratory came from a woman with cervical cancer in 1957.

The cells grew so well and are so robust, they have been used in research to this day.

The life cycle of an organism is closely linked to cell division.

Cell division is important in growth and repair of tissues in multicellular organisms, and in the reproduction of all organisms.

Figure 11.1 Important Consequences of Cell Division

Four events must occur for cell division:

• A reproductive signal initiates cell division

• Replication of DNA

• Segregation: distribution of DNA into two new cells

• Cytokinesis: separation of cellular material into the two new cells

In prokaryotes, binary fission results in two new single-celled organisms.

External factors such as nutrient concentration and environmental conditions are the reproductive signals.

For many bacteria, abundant food supplies speed up the division cycle.

Most prokaryotes have one chromosome, a single molecule of DNA. Often forms a circle, but is compacted and folded.

Two important regions:

• ori—where replication starts (origin)

• ter—where replication ends (terminus)

Replication occurs as the DNA is threaded through a “replication complex” of proteins.

The ori regions move toward opposite ends of the cell, aided by special proteins.

When replication is complete, the daughter DNA molecules are segregated at opposite ends.

In rapidly dividing prokaryotes, DNA replication occupies the entire time between cell divisions.

Figure 11.2 Prokaryotic Cell Division (Part 1)

Cytokinesis begins by a pinching in of the plasma membrane; protein fibers form a ring.

New cell wall materials are synthesized, resulting in separation of the two cells.

Figure 11.2 Prokaryotic Cell Division (Part 2)

In eukaryotes, signals for cell division are related to the needs of the entire organism.

Many cells in multicellular organisms become specialized and seldom divide.

Eukaryotes usually have many chromosomes; replication and segregation are more intricate.

Newly replicated chromosomes are closely associated (sister chromatids).

Mitosis separates them into two new nuclei.

Cytokinesis proceeds differently in animal and plant cells (plants have cell walls).

Cells resulting from mitosis are genetically identical to the parent cell.

Meiosis is nuclear division in cells involved in sexual reproduction.

The cells resulting from meiosis are not identical to the parent cells. It results in new gene combinations.

Cell cycle: period from one cell division to the next; divided into mitosis/cytokinesis and interphase.

Interphase: nucleus is visible and cell functions, including DNA replication, occur; begins after cytokinesis, ends when mitosis starts (M phase).

Duration of interphase is highly variable.

Figure 11.3 The Eukaryotic Cell Cycle

Interphase has three subphases: G1, S, and G2

• G1: between cytokinesis and S phase; chromosomes are single, unreplicated structures.

Duration of G1 is variable, from a few minutes to years. Some cells enter a resting phase (G0).

• At the G1-to-S transition the commitment is made to DNA replication and subsequent cell division. Now called the restriction (R) point.

• S phase: DNA replicates; sister chromatids remain together.

• G2: cell prepares for mitosis (e.g., by synthesizing structures to move the chromatids).

Specific signals trigger the transition from one phase to another.

Identification of these signals came from cell fusion experiments.

For example, cells in the S phase produce a substance that activates DNA replication.

Figure 11.4 Regulation of the Cell Cycle

Working with Data 11.1: Regulation of the Cell Cycle

• To study regulation of the cell cycle, HeLa cells were fused using the membrane-enclosed Sendai virus of mice.

• DNA of cells in the S phase was labeled with radioactive thymidine.

• Cells in S and G1 were then fused and again exposed to radioactive thymidine.

• After fusion, the percent of G1 nuclei that had incorporated new label (had replicated their DNA) was calculated:

• S and G2 cells were then fused in various combinations and the percent of cells in mitosis determined:

• Question 1:

• According to Figure A, how long did it take for all the G1 nuclei in the G1/S cells to become labeled?

• Question 2:

• Examine the data for fused G1/G1 cells and unfused G1 cells in Figure A.

• Explain why these were appropriate controls for the experiments.

• When did these nuclei become labeled?

• Compare these times with each other and with the G1/S nuclei and discuss.

• Question 3:

• Examine the data in Figure B.

• Why did it take longer for the cells in S phase to begin mitosis than it did for the cells in G2?

• Question 4:

• According to Figure B, did fusion with G2 cells alter the timing of mitosis in the S cell nuclei?

• Explain what this means in terms of control of the cell cycle.

The signals act through cyclin-dependent kinases (Cdk’s).

Protein kinases catalyze transfer of a phosphate group from ATP to a protein (phosphorylation). The shape and function of the protein changes.

Cdk’s play important roles in the cell cycle.

Cdk is activated by binding to cyclin (allosteric regulation); this alters its shape and exposes the active site.

There are many different cyclin–cdk complexes acting at different stages of the cell cycle.

Figure 11.5 Cyclin Binding Activates Cdk

Figure 11.6 Cyclin-Dependent Kinases Regulate Progress through the Cell Cycle

At the G1-S transition:

Progress past the restriction point depends on retinoblastoma protein (RB).

RB normally inhibits the cell cycle, but when phosphorylated by G1-S cyclin-Cdk, RB becomes inactive and no longer blocks the cell cycle.

Progress through the cell cycle depends on Cdk activity, so regulating Cdk is a key to regulating cell division.

Cdk’s can be regulated by the presence or absence of cyclins.

Figure 11.7 Cyclins Are Transient in the Cell Cycle

Cyclin–Cdk’s act at cell cycle checkpoints to regulate progress.

Example: At checkpoint R, if DNA is damaged, p21 protein is made.

p21 binds to G1 Cdk’s, preventing their activation.

The cell cycle stops while DNA is repaired.

Table 11.1

The cell cycle is also influenced by external signals.

Some cells divide infrequently or go into G0. They must be stimulated by growth factors to divide.

• Platelet-derived growth factor: from platelets that initiate blood clotting; stimulates skin cells to divide and heal wounds.

• Interleukins and erythropoietin are growth factors that stimulate division and specialization of blood cells.

Growth factors bind to specific receptors on target cells and activate signal transduction pathways that end with cyclin synthesis, thereby activating Cdk’s and the cell cycle.

11.3 What Happens during Mitosis?

DNA molecules are complexed with proteins to form chromatin.

After replication, the sister chromatids are held together during G2 by proteins called cohesins.

At mitosis the cohesin is removed, except at the centromere region. Other proteins called condensins coat the DNA molecules and make them more compact.

Figure 11.8 Chromosomes, Chromatids, and Chromatin

Eukaryotic DNA molecules are extensively “packed” and organized by histones—proteins with positive charges that attract the negative phosphate groups of DNA.

Interactions result in the formation of beadlike units, or nucleosomes.

Figure 11.9 DNA is Packed into a Mitotic Chromosome (Part 1)

Figure 11.9 DNA is Packed into a Mitotic Chromosome (Part 2)

During interphase, the DNA is less densely packed and is accessible to proteins involved in replication.

Once the mitotic chromosome has formed, it is inaccessible to replication and transcription factors.

Mitosis (M phase) ensures accurate segregation of chromosomes to daughter cells.

The phases of mitosis:

• Prophase: chromatin condenses and chromatids become visible

• Prometaphase: nuclear envelope breaks down and chromosomes attach to the spindle

• Metaphase: chromosomes line up at the midline

• Anaphase: chromosomes separate and move to opposite poles

• Telophase: nuclear envelopes reform, spindle disappears, chromosomes become less compact

Figure 11.10 The Phases of Mitosis (Part 1)

The spindle apparatus (or mitotic spindle) moves sister chromatids apart:

• Made of microtubules

• Orientation is determined by the centrosome, an organelle near the nucleus

Each centrosome can consist of two centrioles—hollow tubes formed by microtubules at right angles.

The centrosome doubles during S phase; during prophase, they move to opposite ends of the nuclear envelope.

They identify the “poles” toward which the chromosomes move.

The centrioles are surrounded by tubulin dimers, which will form the spindle apparatus.

Late in prophase, kinetochores develop on each chromatid.

Microtubules form between the poles and the chromosomes to make up the spindle.

Figure 11.11 The Mitotic Spindle Consists of Microtubules

Two types of microtubules in the spindle:

• Polar microtubules form spindle framework; run from one pole to the other.

• Kinetochore microtubules attach to kinetochores on the sister chromatids and to microtubules in opposite halves of the spindle.

During anaphase, separation of sister chromatids is controlled by M phase cyclin–Cdk; it activates anaphase-promoting complex (APC).

Cohesin that holds the chromatids together is hydrolyzed by separase.

Figure 11.12 Chromatid Attachment and Separation

A cell cycle checkpoint (spindle assembly checkpoint) occurs at the end of metaphase.

It inhibits APC if a chromosome is not attached properly to the spindle.

When all are attached, APC is activated and the chromatids separate.

After separation, the chromatids are called daughter chromosomes.

• Chromatids share a centromere.

• Chromosomes have their own centromere.

Two mechanisms move the chromosomes:

• Kinetochores have motor proteins— kinesins and cytoplasmic dynein; energy from ATP moves chromosomes along the microtubules.

• Kinetochore microtubules also shorten, drawing chromosomes toward poles.

Cytokinesis: division of the cytoplasm.

In animal cells the plasma membrane pinches in between the nuclei.

A contractile ring of microfilaments of actin and myosin forms; the proteins interact to contract and pinch the cell in two.

In plant cells, vesicles from the Golgi apparatus appear along the plane of cell division. These fuse to form a new plasma membrane.

Contents of vesicles form a cell plate—the beginning of the new cell wall.

Figure 11.13 Cytokinesis Differs in Animal and Plant Cells

Following cytokinesis, each daughter cell contains all the components of a complete cell.

Organelles such as ribosomes, mitochondria, and chloroplasts do not need to be distributed equally, as long as some are present in each cell.

Table 11.2

Asexual reproduction is based on mitotic divisions.

Unicellular organisms can reproduce by fission; multicellular organisms can also reproduce asexually.

Aspen trees have shoots that sprout from the root system. All the trees in a stand may be clones of a single parent.

Figure 11.14 Asexual Reproduction on a Large Scale

Sexual reproduction: offspring are not identical to the parents.

Requires gametes created by meiosis; two parents each contribute one gamete to an offspring.

Gametes and offspring differ genetically from each other and from the parents. Meiosis generates genetic diversity that is the raw material of evolution.

Somatic cells—body cells not specialized for reproduction.

Each somatic cell contains homologous pairs of chromosomes with corresponding genes. Each parent contributes one homolog.

Gametes contain only one set of chromosomes—one homolog of each pair.

Chromosome number is haploid (n).

Fertilization: two haploid gametes (female egg and male sperm) fuse to form a diploid zygote; chromosome number = 2n.

Evolution has generated many different versions of the sexual life cycle, but:

• all involve meiosis to produce haploid cells;

• fertilization and meiosis alternate;

• haploid (n) cells or organisms alternate with diploid (2n) cells or organisms.

Figure 11.15 Fertilization and Meiosis Alternate in Sexual Reproduction (Part 1)

Sexual reproduction:

• Random selection of half of the diploid chromosome set to make a haploid gamete

• Fusion of two haploid gametes to produce a diploid cell

• Results in shuffling of genetic information in the population

No two individuals have exactly the same genetic makeup (unless they are identical twins).

The diversity provided by sexual reproduction provides enormous opportunities for evolution.

Meiosis consists of two nuclear divisions, but DNA is replicated only once.

• Reduces chromosome number from diploid to haploid.

• Ensures that each haploid product has a complete set of chromosomes

• Generates genetic diversity among the products

Meiosis I:

• Homologous chromosomes pair up;

• The homologous pairs separate, but the individual chromosomes (two sister chromatids), remain intact;

• Is preceded by an S phase in which each chromosome is replicated;

• Results in two nuclei with half of the original chromosomes (one member of each homologous pair).

Figure 11.16 Meiosis: Generating Haploid Cells (Part 1)

During prophase I, the homologous chromosomes pair by adhering along their lengths: synapsis.

The four chromatids of each homologous pair form a tetrad.

In prophase I and metaphase I, chromatin coils and compacts.

At some point, the homologs seem to repel each other but are held together by cohesins at regions called chiasmata that form between nonsister chromatids.

Figure 11.17 Chiasmata: Evidence of Genetic Exchange between Chromatids

Crossing over: exchange of genetic material occurs between nonsister chromatids at the chiasmata.

Crossing over results in recombinant chromatids and increases genetic variability of the products.

Figure 11.18 Crossing Over Forms Genetically Diverse Chromosomes

Meiosis can take a long time to complete.

• Human males: prophase I lasts about a week, and the entire meiotic cycle takes about a month.

• Human females: prophase I begins before birth and ends up to decades later, during the monthly ovarian cycle.

In meiosis I maternal chromosomes pair with paternal homologs during synapsis.

This does not occur during mitosis.

Meiosis I guarantees that each daughter nucleus gets one full set of chromosomes.

Crossing over is one reason for genetic diversity in meiosis I products.

In anaphase I, independent assortment also allows for chance combinations.

• It is a matter of chance how the homologous chromosomes line up and which ones go to which daughter cell.

The greater the number of chromosomes, the more combinations that are possible, and the greater the potential for genetic diversity.

Humans have 23 pairs of chromosomes. 223 (8,388,608) different combinations can be produced just by independent assortment.

Meiosis II:

• Not preceded by DNA replication

• Sister chromatids are separated

• Chance assortment of the chromatids contributes further to the genetic diversity.

• Final products are four haploid daughter cells (n).

Figure 11.19 Mitosis and Meiosis: A Comparison (Part 1)

Figure 11.19 Mitosis and Meiosis: A Comparison (Part 2)

There can be errors in meiosis:

Nondisjunction:

• Homologous pairs fail to separate at anaphase I; or

• In meiosis II, sister chromatids fail to separate

Results in aneuploidy—chromosomes are lacking or present in excess.

Figure 11.20 Nondisjunction Leads to Aneuploidy

Aneuploidy may be caused by lack of cohesins that hold the homologous pairs together.

Without cohesins both homologs may go to the same pole.

The resulting gametes will have two of the same chromosome or none.

In humans, Down syndrome results from a gamete with two copies of chromosome 21. After fertilization, there are three copies (trisomic).

A fertilized egg that did not receive a copy of chromosome 21 will be monosomic, which is lethal.

Trisomies and monosomies are common in human zygotes.

Most embryos from these zygotes do not survive.

Trisomies and monosomies for chromosomes other than 21 are lethal—many miscarriages are due to this.

Translocation: a piece of chromosome may break away and attach to another chromosome.

An individual with a translocated piece of chromosome 21 plus two normal copies will have Down syndrome.

When cells are in metaphase of mitosis, it is possible to count and characterize the chromosomes.

The karyotype is the number, shapes, and sizes of all the chromosomes of a cell.

Karyotypes can be used to diagnose abnormalities such as trisomies, a branch of medicine called cytogenetics.

Figure 11.21 The Human Karyotype

Organisms with complete extra sets of chromosomes are called polyploid.

Triploid (3n), tetraploid (4n), and even higher levels are possible.

If there is nondisjunction of all chromosomes during meiosis I, diploid gametes will form, leading to autopolyploidy after fertilization.

Autotriploids and autotetraploids have been important in some species formation.

Diploid and other even numbered polyploid cells can undergo meiosis— chromosomes can pair with their homologs.

Triploids cannot undergo meiosis and are usually sterile.

Polyploid cells tend to be larger and are favored as crop plants. Bananas and seedless watermelons are triploid.

In wheat, hybridization between species produced allopolyploids.

Modern bread wheat arose from three different species and two episodes of nondisjunction that led to a hexaploid.

Figure 11.22 Polyploidy and the Origin of Bread Wheat (Part 1)

Figure 11.22 Polyploidy and the Origin of Bread Wheat (Part 2)

Cell death occurs in two ways:

1. Necrosis—cell is damaged or starved of oxygen or nutrients. The cell swells and bursts.

Cell contents are released to the extracellular environment and can cause inflammation.

2. Apoptosis is genetically programmed cell death. Two possible reasons:

• The cell is no longer needed (e.g., connective tissue between the fingers of a fetus).

• Old cells are prone to genetic damage that can lead to cancer. Epithelial cells may be exposed to radiation and toxins; they live only days or weeks.

Events of apoptosis:

• Cell detaches from its neighbors

• Chromatin is digested by enzymes that cut DNA between nucleosomes

• Forms membranous lobes called “blebs” that break into fragments

• Surrounding living cells ingest remains of the dead cell and recycle the contents

Figure 11.23 Apoptosis: Programmed Cell Death (Part 1)

In plants, a defense mechanism called the hypersensitive response involves apoptosis.

Cells at the site of a bacterial or fungal infection die and prevent spread through living cells.

Signals that initiate apoptosis: hormones, growth factors, viral infections, toxins, extensive DNA damage.

The signals act through signal transduction pathways.

Some pathways affect mitochondria, increasing permeability of the membranes. ATP production stops and the cell dies.

Proteases called caspases may be activated in apoptosis.

Caspases hydrolyze membrane proteins in nuclear and cell membranes and nucleosomes.

Figure 11.23 Apoptosis: Programmed Cell Death (Part 2)

Cancer is the number two cause of death in the United States and involves inappropriate increases in cell numbers.

Cancer cells differ from normal cells:

• They lose control over cell division.

• They can migrate to other parts of the body.

Normal cells divide in response to extracellular signals such as growth factors.

Cancer cells divide almost continuously, forming tumors, large masses of cells.

Benign tumors resemble the tissue they grow from, grow slowly, and remain localized.

They are not cancerous but must be removed if they obstruct an organ or function.

Malignant tumors do not resemble the parent tissue.

The cells often have irregular structures that can be used to identify the cells as malignant.

Figure 11.24 A Cancer Cell with its Normal Neighbors

Metastasis:

Cancer cells can invade surrounding tissue and travel through the bloodstream or lymph system.

Wherever the cancer cells lodge, they continue dividing and form new tumors. This results in organ failures and makes cancers difficult to treat.

In normal cells, the cell cycle is regulated by proteins:

• Positive regulators such as growth factors stimulate cell division.

• Negative regulators such as retinoblastoma protein (RB) inhibit the cell cycle.

Oncogene proteins: positive regulators in cancer cells.

Normal regulators are mutated to be overactive or present in excess.

Example: DNA changes that increase production of the growth factor receptor HER2 in breast tissue may result in rapid cell proliferation.

Figure 11.25 Molecular Changes in Cancer Cells (Part 1)

Tumor suppressors: negative regulators such as RB, which are inactive in cancer cells.

Some viruses inactivate tumor suppressors. Human papillomavirus produces a protein that blocks RB.

Figure 11.25 Molecular Changes in Cancer Cells (Part 2)

p53 is a transcription factor involved in cell cycle checkpoints.

More than 50% of human tumors have mutations in the gene that encodes p53.

The discovery of apoptosis changed the way biologists think about cancer.

In normal, nongrowing tissue, the rate of cell division equals the rate of apoptosis.

Cancer cells are defective in their regulation of the cell cycle, resulting in increased division rates as well as lower apoptosis rates.

Surgical removal of tumors is the optimal treatment, but sometimes not all cancer cells can be removed.

Other treatments target the cell cycle:

• Drugs that prevent cell division: 5-fluorouracil blocks synthesis of thymine (a DNA base); paclitaxel prevents functioning of microtubules in the mitotic spindle.

• Radiation treatment causes DNA damage in tumor cells, repair mechanisms are overwhelmed and the cells undergo apoptosis.

These treatments target normal cells as well; research is ongoing to find treatments that affect only cancer cells.

Herceptin targets the HER2 growth factor receptor involved in some breast cancers.

Herceptin binds to the receptor but does not stimulate it; prevents the natural growth factor from binding.

Figure 11.26 Cancer Treatment and the Cell Cycle

11 Answer to Opening Question

HeLa cells have a genetic imbalance that heavily favors cell reproduction over cell death.

The cells originally came from a cervical tumor caused by human papillomavirus, which stimulates cell division.

11 Answer to Opening Question

Also, the enzyme telomerase, which keeps DNA intact and prevents cell death, is overexpressed in HeLa cells.

Thus HeLa cells have a combination of high cell division rates and decreased apoptosis.

11 The Cell Cycle and Cell Division. 11 The Cell Cycle and Cell Division 11.1 How Do Prokaryotic and...

Documents

Transcript of 11 The Cell Cycle and Cell Division. 11 The Cell Cycle and Cell Division 11.1 How Do Prokaryotic and...

Cell cycle & it’s regulation - Patna Women's College · Topic- Eukaryotic cell cycle and Regulation of cell cycle Faculty name- Dr Pinky Prasad Email- dr.pinky.prasad@gmail.com

CELL CYCLE Interphase, Mitosis, Cytokinesis. The cell cycle is a repeated pattern of growth and division that occurs in eukaryotic cells. This cycle consists.

Regulating the Cell Cycle...The cell cycle is controlled by regulatory proteins both inside and outside the cell. Cyclins proteins that regulate the timing of the cell cycle in eukaryotic

1.2 Eukaryotic Cell Growth and the Cell Cycle Two Stages: INTERPHASE – G 1, S, G 2 MITOSIS (incl. CYTOKINESIS) 1.2 Cell Growth and the Cell Cycle.

Schematic of the Cell Cycle of Eukaryotic Cells

Eukaryotic Cells and the Cell Cycle - Offices and - umb.edufaculty.umb.edu/yvonne_vaillancourt/111sp2013/Lab 8, Cell cycle... · Identify the stages of the cell cycle. ... meiosis

The Eukaryotic cell cycle and Mitosis - Groby Bio Pagegrobybio.weebly.com/uploads/2/6/2/3/26235017/076... · 2019-10-29 · The eukaryotic cell cycle and mitosis Bio Factsheet 2 Prophase

Prokaryotic cell reproduction Binary Fission. Eukaryotic Cell Cycle.

Eukaryotic Cell Eukaryotic Cell organelles and structure Eukaryotic Cell.

Cell Growth and Reproduction. 1. The Cell Cycle A.The cell cycle involves the growth, replication, and division of a eukaryotic cell. B.The two main phases.

The Eukaryotic Cell Cycle : Molecules, Mechanisms, and Mathematical Models

Regulating the Eukaryotic Cell Cycle

The Eukaryotic cell cycle and Mitosis

Chapt. 16 Eukaryotic Cell cycle; Chapt. 17 Stem cells Chapt. 16 Student learning outcomes: Explain basic phases of eukaryotic cell cycle Regulators, checkpoints.

Lesson Objectives Contrast cell division in prokaryotes and eukaryotes. Identify the phases of the eukaryotic cell cycle. Explain how the cell cycle.

Analysis of a Generic Model of Eukaryotic Cell-Cycle Regulation · 2010. 2. 1. · Analysis of a Generic Model of Eukaryotic Cell-Cycle Regulation Attila Csika´sz-Nagy,*y Dorjsuren

Eukaryotic Cell Cycle Cell cycle: repeating sequence of cellular growth and division during the life of the cell – Interphase – Mitosis – Cytokinesis.

Molecular Cell Biology Lodish 6th.ppt - Chapter 20 regulating the eukaryotic cell cycle

10.2 Eukaryotic Cell Cycle

Cell cycle and cell apoptosis · 2017. 10. 23. · The cell cycle and cellular proliferation •Process by which eukaryotic cells duplicate and divide. •Interphase, consisting of