The Cell Cycle

Chapter 12

Cells have to divide in order to multiply

Why Cells Divide?

Reproduction of a single celled organism (asexual reproduction )

Growth & development Tissue repair/ growth & replacement To maintain a favourable Surface area to

volume ratio

Cell cycle Life of a cell from origin

to division into 2 new daughter cells

Who are the players: Nucleus

chromosomes DNA

Cytoskeleton Centrioles (in animals) microtubule spindle fibers

Nucleus Function

protects DNA Structure

nuclear envelope double membrane membrane fused in spots to create pores

allows large macromolecules to pass through

histone protein

chromosome

DNA

Cytoskeleton Function

structural support maintains shape of cell provides anchorage for organelles

protein fibers microfilaments, intermediate filaments, microtubules

motility cell locomotion cilia, flagella, etc.

regulation organizes structures

& activities of cell

Centrioles Cell division

in animal cells, pair of centrioles organize microtubules

spindle fibers guide chromosomes in mitosis

Cell division Distribution of identical genetic material -

packaged as DNA (genome) - to two daughter cells Prokaryotes, the genome is often a single long

DNA molecule. Eukaryotes, the genome consists of several

DNA molecules. DNA is passed along, without dilution, from one

generation to the next A dividing cell duplicates its DNA, allocates

the two copies to opposite ends of the cell, and then splits into two daughter cells

Chromosomes

DNA molecules are packaged into chromosomes

Every eukaryotic species has a characteristic number of chromosomes in the nucleus.

Human somatic cells (body cells) have 46 chromosomes.

Human gametes (sperm or eggs) have 23 chromosomes, half the number in a somatic cell

Chromosomes Eukaryotic chromosome consists of a long,

linear DNA molecule has hundreds or thousands of genes, the units that specify an organism’s inherited traits

Associated with DNA are proteins that maintain its structure and help control gene activity

This DNA-protein complex, chromatin, is organized into a long thin fiber.

After the DNA duplication, chromatin condenses, coiling and folding to make a smaller package

Copying DNA & packaging it…

After DNA duplication, chromatin condenses coiling & folding to make a smaller package

DNA

chromatin

mitotic chromosome

Distribution of Chromosome Duplicated chromosome

2 sister chromatids narrow at centromeres contain identical

copies of original DNAhomologous

chromosomeshomologous

chromosomes

sister chromatidshomologous = “same information”

single-strandeddouble-stranded

Mitosis and Cytokinesis

Mitosis formation of the two daughter nuclei

Cytokinesis division of the cytoplasm

These processes take one cell and produce two cells that are the genetic equivalent of the parent

Cell Division in Sex cells (Gametes)

Humans 23 pairs of chromosomes from each parent: one set in an egg and one set in sperm.

Gametes (eggs or sperm) are produced only in gonads (ovaries or testes)

In the gonads, cells undergo a variation of cell division, meiosis, which yields four daughter cells, each with half the chromosomes of the parent.

In humans, meiosis reduces the number of chromosomes from 46 to 23.

Fertilization fuses two gametes together and doubles the number of chromosomes to 46 again.

The Cell Cycle

An orderly sequence of events that extends from the birth of a cell till the time it divides itself

All Eukaryotic cells undergo this cycle Cycle is divided into

InterphaseMitotic Phase

The Cell Cycle

Interphase 90% of the Cell Cycle

1. G1(gap)phase: cell spends most of its functional life. Gap bet. DNA syn

& cell div Cell grows,

protein & organelles synthesized

Interphase contd. S-Phase the DNA

synthesis phase. DNA molecules are

copied or replicated, single stranded DNA in G1 phase to double stranded DNA in G2.

G2 Phase completion of DNA syn. & onset of cell division

Mitotic Phase Division of the nucleus plus

cytokinesis, produces two identical daughter cells

StagesProphaseMetaphaseAnaphaseTelophase

Interphase is not part of mitosis, it encompasses stages G1, S, and G2 of the cell cycle.

Interphase

Chromatin not visible

DNA replicated New organelles are

formed cell grows by

producing proteins and cytoplasmic organelles

prepares for cell division.

Prophase Chromosomes

condensed and visible with sister chromatids joined together

The nucleoli disappear

Centrioles at opposite poles of cell

The mitotic spindle begins to form

Phase ends with the breakdown of the nuclear membrane

Transition to Metaphase Prometaphase

spindle fibers attach to centromeres

creating kinetochores microtubules attach at

kinetochores connect centromeres to

centrioles chromosomes begin

moving

Metaphase The second stage Chromosomes

gather in the a plate across the middle of the cell

Mitotic spindle is fully formed

All chromosomes are attached to the spindle microtubules

Anaphase The third stage of

mitosis The sister

chromatids suddenly separate from their partners.

Each chromatid daughter chromosomes move toward the poles

Microtubules shorten, bringing the chromosomes closer to the poles.

Kinetochores use motor proteins that “walk” chromosome along attached microtubulemicrotubule

shortens by dismantling at kinetochore (chromosome) end

Chromosome Movement

Telophase The final stage of mitosis The chromosomes reach

the poles of the spindle. This processes is the

reverse of prophase spindle disappears, nuclear envelopes reform, the chromosomes uncoil and lengthen, and nucleoli reappear.

Mitosis, the division of one nucleus into two

genetically identical daughter nuclei, is now finished.

Cytokinesis Division of the cytoplasm Occurs along with telophase Two daughter cells separate Difference in animal and plant cells

Animal Cell cell membrane pinches off to form a cleavage furrow

Plant Cell Cell plate is formed to divide cell into two

Animal Cell Animals

constriction belt of actin microfilaments around equator of cell

cleavage furrow forms

splits cell in two like tightening a

draw string

Plant Cell Plants

cell plate forms vesicles line up at

equator derived from Golgi

vesicles fuse to form 2 cell membranes

new cell wall laid down between membranes

new cell wall fuses with existing cell wall

Plant Cell

Binary Fission

Reproduction of Bacteria and Archae

Evolution of mitosis A possible

progression of mechanisms intermediate between binary fission & mitosis seen in modern organisms

Regulation of the Cell Cycle

What drives the process? Evidence supports that it is specific

chemicals present in the cytoplasm

Cell Cycle Control System

A cyclically operating set of molecules that triggers key events

Analogous to a washing machine control panel

Checkpoints Cell cycle controlled

by STOP & GO chemical signals at critical points

Signals indicate if key cellular processes have been completed correctly

Located at end of G1, G2 and M

G1 checkpoint

G1 checkpoint is most critical primary decision point if cell receives

“GO” signal, it divides internal signals: cell growth (size), cell

nutrition external signals: “growth factors”

if cell does not receive signal, it exits cycle & switches to G0 phase

non-dividing, working state

G0 phase

MMitosis

G1Gap 1

G0Resting

G2Gap 2

SSynthesis

G0 phasenon-dividing, differentiated statemost human cells in G0 phase liver cells

in G0, but can be “called back” to cell cycle by external cues

nerve & muscle cells highly specialized arrested in G0 & can

never divide

“Go-ahead” signals Protein signals that promote cell

growth & division internal signals

“promoting factors”external signals

“growth factors”

Primary mechanism of controlphosphorylation

kinase enzymes either activates or inactivates cell signals

Cell Cycle Signals Cell cycle controls

cyclins regulatory proteins Fluctuates during cell cycle

Cdks at a constant concentration cyclin-dependent kinases phosphorylates cellular proteins

activates or inactivates proteins

Cdk-cyclin complex Will phosphorylate messenger

compounds

M- Checkpoint

Internal checkpoint Anphase does not begin till chromosomes

are hooked to spindle If kinetochores are not correctly attached

anaphase promoting complex is kept inactive

If correctly attached releases proteolytic enzymes that break down cyclin and centromere proteins

Control of Cell Division

Growth FactorsPlatelet derived growth factor

Density dependent inhibition Anchorage dependence

Growth Factors Coordination between cells

protein signals released by body cells that stimulate other cells to divide

Body has many different types Each stimulates only cells with that

type of receptor PDGF stimulates fibroblasts

Density dependent inhibition

Cultured cells normally divide until they form a single layer on the inner surface of the culture container

If a gap is created, the cells will grow to fill the gap.

Anchorage dependence

Cells must be anchored to a substratum, typically the extracellular matrix of a tissue.

Cancer cells are free of both density-dependent inhibition and anchorage dependence.

What Causes Cancer? Cells do not have a properly

functioning “cell cycle” control system

Cells divide excessively and result in an abnormal mass of cells

Tumors and Cancer Benign mass of normal cells

Can be removed surgicallyAlways remain at their original site

MalignantMass of cancer cellsSpread to other tissues by entering

the circulatory system Metastasis spread of cancer

cells beyond site

Metastasis Malignant tumors invade surrounding

tissues and can metastasize Exporting cancer cells to other parts of

the body where they may form secondary tumors

Cancer cells invade neighboring tissue.

2 A small percentage of cancer cells may survive and establish a new tumor in another part of the body.

4Cancer cells spread through lymph and blood vessels to other parts of the body.

3A tumor grows from a single cancer cell.

1

Tumor

Glandulartissue

Cancer cell

Bloodvessel

Lymphvessel

MetastaticTumor

Figure 12.19

Types of Cancer Carcinoma external or internal

coverings of the body-skin, intestinal linings

Sarcoma bone and muscle Leukemia and Lymphoma- blood

forming tissues

Treatment of Cancer Surgery Radiation therapy high energy

radiation disrupts cell division Chemotherapy drugs that inhibit

cell division Side effects:

Radiation can lead to sterilityChemotherapy can cause nausea,

hair loss

Growth Factors and Cancer Growth factors can create cancers

proto-oncogenes normal growth factor genes that become

oncogenes (cancer-causing) when mutated

stimulates cell growth if switched “ON” can cause cancer example: RAS (activates cyclins)

tumor-suppressor genes inhibits cell division if switched “OFF” can cause cancer example: p53