Chapter 12 The Cell Cycle

Outline

• Purposes of Cell Division

• Cell Division in Eukaryotes

– Chromosomes and the Genome

– Phases of the Cell Cycle

– Mitosis

– Cytokinesis

• Cell Division in Prokaryotes

• Control of the Cell Cycle

Why do Cells Divide?

• Three key reasons:

Figure 12.2a Reproduction

Figure 12.1b Growth and development

Figure 12.1c Tissue renewal

Cell Division in Eukaryotes

The Genome

• Genome: The genetic material (DNA) of an organism.

– The key portion of the genome is found within the nucleus

– Mitochondria, chloroplasts and centrioles contain small genomes.

• Individual DNA/protein strands are called Chromosomes

• The DNA strands are bound to proteins and collectively termed Chromatin

– 40% DNA and 60% protein

Chromosomes

• Eukaryotic DNA comes as linear chromosomes.

• The term chromosome is also used to describe the condensed state of each DNA molecule that occurs during cell division.

• Almost all genes are found on the chromosomes

Packaging of DNA into Chromosomes

• DNA is packaged around proteins called histones, and wound tightly into condensed coils.

The Anatomy of a Chromosome

Fig. 12.4

Chromosome Karyotypes

• Chromosomes have visible differences

– Size

– Staining properties

– Banding pattern

– Position of the centromere

– Position of other constrictions

• Karyotype: the particular array of chromosomes that an individual possesses

Figure 12.5 The cell cycle

Cell Cycle

• Eukaryotic cells that divide undergo a cell cycle.

– This is simply an orderly sequence of events that starts from when the cell is first produced to when it divides.

– It ensures that each step is properly completed before moving to the next step.

– Highly specialized cells such as muscle and nerve cells lose their ability to divide on reaching maturity.

These orderly sequence of events are
divided into Phases (Fig 12.5)

Cell Cycle

• 90% of the time the cell is in Interphase

• Interphase consists of three phases called G₁, S & G_2.

• During Interphase the cell:

– Expands its size by increasing its cytoplasm; proteins & organelles

– Replicates its genome

– Differentiates

• becomes specialized for its function

– Metabolizes

– Performs its specialized function

• M phase or Mitotic Phase, consists of two overlapping processes

– Mitosis: divides the nucleus & duplicated chromosomes.

– Cytokinesis: divides the cytoplasm in two.

• G₁: primary growth phase, preparation for DNA replication

• S: a replica of the genome is synthesized

• G₂: second growth phase, Proteins needed in mitosis are synthesized

• M: Mitosis (or meiosis) division of the nucleus, Cytokinesis – division of the cytoplasm

Duration of the Cell Cycle

• Accelerated in growing embryos

– ~ 20 minutes

– Do not grow in size, cells become progressively smaller

• Mature cells have longer cell cycles

– 24 hours, 1 year

• Non-dividing cells pause in G₁ and enter a resting state called G₀.

– Can remain in G₀ permanently

Eukaryotic cells and genomes are much larger than prokaryotic, so the process for dividing the chromosomes between the daughter cells is very complex.

Mitosis

• Dividing of the chromosomes (nuclear division)

• Each daughter cell will get a complete genome.

Stages of Mitosis

• Prophase

• Prometaphase

• Metaphase

• Anaphase

• Telophase

Interphase

• Interphase consists of the G1, S and G2 parts of the cell cycle – not mitosis.

• The nuclear envelope surrounds the nucleus.

• Two centrosomes have formed by replication of a single centrosome.

• The chromosomes have duplicated, during S phase, but are still in the form of chromatin and cannot be seen individually.

Prophase

• Chromatin fibers condense into discrete observable chromosomes.

• Nucleoli disappear

• The mitotic spindle is assembled

Assembly of the Mitotic Spindle

• The mitotic spindle consists of fibers made of microtubules and associated proteins.

• Assembly starts at the centrosome, which is a microtubule organizing center.

• By the end of prometaphase, the two centrosomes, face opposite each other, with one at each pole of the cell.

• The spindle microtubules come out from each centrosome.

Attachment of the spindle fibers to the chromosomes

• Each of the two sister chromatids of a chromosome has a kinetochore attached.

• This is a structure of proteins that is the attachment site for the microtubule.

• Once the spindle fiber is attached to the kinetochore, the chromosome can be pulled.

Prometaphase

• The nuclear envelope dissolves.

• Kinetochores begin to mature and attach to spindle

– sister chromatids will become linked to opposite poles

Metaphase

• Chromosomes align at the ‘metaphase plate” (down the middle of the cell)

• Kinetochores of the sister chromatids are linked to opposite poles via microtubules.

Fig 12.7

Anaphase

• Kinetochore microtubule shorten

• Polar microtubules elongate

• Sister chromatids are separated and move to opposite poles.

Telophase

• Chromosomes reach cell poles

• Kinetochores disappear

• Polar microtubules continue to elongate, preparing cell for cytokinesis

• Nuclear membranes reform

• Chromosomes decondense into chromatin

Mitosis Animation

Cytokinesis

• Plant cells: cell plate forms, dividing daughter cells

• Animal cells: cleavage furrow made of actin filaments forms at equator of cells and pinches inward until cell divides in two.

Figure 12.9 Cytokinesis in animal and plant cells

Cell Division in Prokaryotes

• Bacterial genome is a single circular, DNA molecule.

– Attached to the plasma membrane

– Replication origin controls replication of the DNA

Cell Division in Prokaryotes

• Mechanism of cell division is called binary fission.

– Cell grows to about 2X normal size

– DNA is replicated

– Cell membrane and cell wall are assembled between the attachment sites of replicated DNA molecules, dividing the cell into two cells.

Figure 12.11 Bacterial cell division

Cell Cycle Control

• Events of the cell cycle are highly controlled and coordinated.

• Evolutionarily conserved among all eukaryotic kingdoms.

• Cell cycle checkpoints ensure that each phase is properly completed before the next phase begins.

Figure 12.13 Mechanical analogy for the cell cycle control system

Molecular Mechanisms of Cell Cycle Control

• The sequential events of the cell cycle come about because of cyclic fluctuation in the abundance and activity of cell cycle control molecules.

• Cyclin-dependent protein kinases (Cdks) phosporylate key enzymes and other proteins in order to activate them and allow progression to the next phase of the cell cycle.

• Cyclins are proteins that bind to Cdks and activate them.

• Each check point is regulated by a different set of kinases.

• For example, entry into M phase is controlled by the G₂ checkpoint.

• Cdk is present at a set level in the cell.

• Cyclin concentration gradually increases until it is at high enough concentration to bind to Cdk.

• Cdk and cyclin together are called MPF “M phase promoting factor”. The Cdk is now active, and phosphorylates/activates other proteins causing M-phase to begin.

• Later in M-phase, cyclin is destroyed, and the cycle is reset.

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External Control of the Cell Cycle

• Growth factors and cell proliferation signaling pathways tell cells when to divide.

Figure 12.17 The effect of a growth factor on cell division

Cancer Cells Growing out of control

• The sequential events that make up the cell cycle are directed by a Cell-Cycle Control System

• Errors in this system can lead to Benign tumors

Cancer Cells

• Both types of tumor displace normal tissue as they grow.

• The most dangerous attribute of cancer cells is their ability to spread into neighboring tissue through the circulatory system.

• The spread of cancer cells beyond their original site is called- Metastasis.

• Both Radio & Chemotherapy attempt to disrupt cell division in the cancerous cells.

Figure 12.19 The growth and metastasis of a malignant breast tumor

Cancer cells do not respond normally to the body’s control mechanisms.

The End.