Mitosis.ppt

Key Concepts

In eukaryotes, most dividing cells go through a cycle that consists of four phases.

After chromosomes are copied during S phase, they are moved to the middle of the cell during M phase (mitosis). One chromosome copy is distributed to each of two daughter cells. Mitosis and

Key Concepts

Progression through the cell cycle is carefully controlled.

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 usually accompanied by

Contrasting Mitosis and Meiosis

• Meiosis leads to the 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.}

Functions of Mitosis

• Mitosis and cytokinesis are responsible for three key events in multicellular eukaryotes:

1. Growth

2. Wound repair

What Is a Chromosome?

• Chromosomes contain a single long double helix of

deoxyribonucleic acid (DNA) wrapped around proteins.

– _{DNA encodes the cell’s genetic information.}

– A gene is a section of DNA that encodes a specific protein or RNA.

Chromosomes Change before and during Mitosis

cells during cell division.

– _{To this end, each chromosome is replicated prior to mitosis.}

• As mitosis starts, the chromosomes condense from long, thin

filaments into compact structures that can be moved around the cell efficiently.

Chromosome Replication

• Prior to 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.

– Chromatids from the same chromosome are referred to as

sister chromatids.

M Phase and 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.

• A visualization technique called autoradiography allowed

researchers to identify the part of the cell cycle during which DNA replication occurs.

• Chromosome replication occurs only during interphase and not during M phase.

– The stage in which DNA replication occurs is called the

Interphase – Gap Phases

• Interphase also includes two gap phases, during which no DNA synthesis occurs.

– _{The first gap, G1 phase, occurs before the S phase.}

– _{The second gap, G2 phase, occurs between S phase and}

mitosis.

• During the gap phases, organelles replicate and 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.

The Cell Cycle

There are a total of four phases in the cell cycle: M phase and an interphase consisting of the G₁, S, and G₂ phases.

Mitosis Overview

• Mitosis results in the division of replicated chromosomes and

formation of two daughter nuclei with identical chromosomes and genes.

– _{Mitosis is usually accompanied by cytokinesis.}

• Every species has a characteristic number of 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.}

• During interphase, most chromatin is “relaxed” or uncondensed, forming long, threadlike strands.

• After replication during S phase, each chromosome consists of two genetically identical sister chromatids attached at the centromere.

Events in Mitosis

During mitosis, the two sister chromatids separate to form

independent chromosomes, and one copy of each chromosome goes to each of the two daughter cells. As a result, each daughter cell receives a copy of the genetic information that is contained in each chromosome.

• Mitosis (M phase) is a continuous process with five subphases based on specific events:

– Prophase

– _Prometaphase – _Metaphase

– Anaphase

Prophase

• During prophase, chromosomes condense and first become visible in the light microscope.

• The mitotic spindle, if 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.

• In animal cells, the microtubule-organizing center is a centrosome

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

Metaphase

• During metaphase, the 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.

Anaphase

• During anaphase, centromeres split and 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 de-condense.

Cytokinesis

• Cytokinesis typically occurs immediately after mitosis. During this process, the cytoplasm divides to form two daughter cells, each

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.

How Do Chromosomes Move during Mitosis?

• Kinetochore microtubules remain stationary during anaphase; they shorten because tubulin subunits of the microtubules are lost from their plus ends at the kinetochore.

• Dyneins and other kinetochore motor proteins are attached to the kinetochore’s fibrous crown and “walk” toward the minus end of the spindle fiber.

Control of the Cell Cycle

• Cell-cycle length can vary greatly among cell types; variation in the length of G₁ phase is responsible for these differences.

– G₁ phase is essentially eliminated in rapidly dividing cells.

– Nondividing cells get permanently stuck in G₁ phase; this arrested stage is called the G₀ state.

• The rate of cell division can also respond to changes in environmental conditions.

Mitosis-Promoting Factor Induces Mitosis

• Mitosis-promoting factor (MPF) is present in the cytoplasm of M-phase cells and induces mitosis in all eukaryotes.

• MPF is composed of two distinct subunits: a protein kinase and a cyclin.

– The protein kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to a target protein

(phosphorylation).

Cyclin Concentration Regulates MPF Concentration

• The concentration of MPF cyclin increases during interphase, then peaks in M phase before decreasing again.

MPF Activation

• After it binds to cyclin, MPF’s Cdk subunit becomes phosphorylated at two sites, rendering it inactive.

• Late in G₂ phase enzymes cause one of the phosphate groups on the Cdk subunit to drop off.

– This dephosphorylation reaction changes MPF’s shape, activating it.

MPF Deactivation

Cell-Cycle Checkpoints

• Many other protein complexes are involved in regulating the cell cycle.

There are three distinct cell-cycle checkpoints during the four

G

Checkpoint

• The first and most important checkpoint occurs late in G₁. This checkpoint determines whether the cell will continue through the cycle and divide, or exit the cycle and enter G₀.

• Four factors affect whether cells pass the G₁ checkpoint:

1. Cell size

2. Nutrient availability

Will a Given Cell Pass the G

Checkpoint?

• Cells must be large enough to split into two functional daughter cells.

• Food must be sufficient for cell growth.

• Cells in multicellular organisms pass (or do not pass) through the G₁ checkpoint in response to signaling molecules from other cells.

• The p53 protein either pauses the cell cycle or initiates apoptosis – programmed cell death – if the DNA is physically damaged.

G

Checkpoint

• The second checkpoint is between the G₂ and M phases. Cells stop growing here if chromosome replication has not proceeded

Metaphase Checkpoint

• The third and final checkpoint is during M phase.

– Cell growth ceases during metaphase if the chromosomes are not properly attached to the mitotic spindle.

– _{This mechanism prevents incorrect chromosome separation}

that could give daughter cells the wrong number of chromosomes.

Cancer: Out-of-Control Cell Division

• Cancer is a common, sometimes lethal disease that affects many humans.

• Cancer is a complex family of diseases caused by cells that grow in an uncontrolled fashion, that invade nearby tissues, and that spread to other sites in the body.

• Cancers vary widely in time of onset, growth rate, seriousness, and cause.

Types of Cancerous Cell Defects

• Cancerous cells have two types of defects:

1. Defects that make the proteins required for cell growth active when they should not be

Properties of Cancer Cells

• A tumor forms when one or more cells in a multicellular organism begin to divide in an uncontrolled fashion.

– _{Benign tumors are noninvasive and noncancerous.}

– Malignant tumors are invasive. They can spread throughout the body via the blood or lymph, and initiate secondary tumors.

Cancer Involves Loss of Cell-Cycle Control

Social Control

• Cells respond to signals from other cells, so that cells divide only when their growth benefits the whole organism. This is known as

social control.

• Social control is based on growth factors–polypeptides or small proteins released by cells that stimulate division in other cells.

– Generally, cell cultures will not grow unless growth factors

are present.

Social Controls and Cell-Cycle Checkpoints

• Rb protein enforces the G₁ checkpoint, keeping the cell in G₀.

• Excessive growth factors can override the inhibitory effects of Rb.

– Cyclin synthesis is triggered and cyclin-Cdk complexes are activated, leading to activation of the S-phase proteins.

• In some human cancers, the G₁ cyclin is overproduced, permanently activating Cdk, which then continuously phosphorylates its target proteins.

Cancer Is a Family of Diseases

• Many different types of defects can cause the G₁ checkpoint to fail.

• Most cancers result from multiple defects in cell-cycle regulation.

– Most cancers develop only after several genes have been damaged.

– _{The combined damage is enough to break cell-cycle control}

and induce uncontrolled growth and metastasis.