chapter 12: cell cycle. chromosome sorting the goal of cell division typically is to equally...

Chapter 12: Cell Cycle

Chromosome Sorting• The goal of cell division typically is to equally

partition two more-or-less identical copies of genetic material between two daughter cells

• Prokaryotes are comparatively simple, with only one chromosome, so have a relatively easy time sorting daughter chromosomes to daughter cells

• Eukaryotes, with their longer DNA and multiple chromosomes, don’t have it nearly so easy

• Much of the complex “dance” of Mitosis is a consequence of the need to make sure that each daughter cell ends up with the same number and type of chromosomes as the parent

Cell Division• Important roles of cellular

division:– Reproduction: Forms duplicate

offspring (amoeba).– Growth and Development:

Allows single cell to form into multicelluar organism

– Tissue Renewal: Cells are damaged and die all the time. These cells need to be replaced.

Prokaryotic Reproduction Through Mitosis

Chromosomal DifferencesProkaryote Chromosome Eukaryote Chromosome

Here “chromosome”and “DNA” are not100% synonymous

Chromosomes vs. Chromatin• Chromosomes

• Tightly packaged DNA• Found only during cell

division• DNA is not being used for

macromolecule synthesis

• Chromatin

• Unwound DNA• Found throughout

Interphase• DNA is being used for

macromolecule synthesis

Eukaryotic Chromosomes

Though chromosomes are“all about” DNA, in fact much this structure consists ofprotein

Formed via replication, not by formed chromatids coming together

How Long is a Chromatid??

• A chromatid is a chromatid as long as it is held in association with a sister chromatid at the centromere

• When two sister chromatids separate (after metaphase) they go from being a single chromosome to being two different chromosomes

Chromosome

Chromatid

Sister Chromatids

Eukaryotic Chromosome

Genome = DNA

Chromosomes = DNA + PROTEIN(visible under light

microscope)

Chromatin = DNA + PROTEIN

(unwound)DNA

Important Vocabulary

• Centromere• Centrosome• Centriole• Kinetochore• Kinetochore microtubules• Mitotic spindle• Nonkinetochore microtubules• Spindle apparatus• Spindle fibers



Nonmembranous organelles that

organize microtubules

throughout the cell cycle

2 Centrioles = Centrosome



Comprised of microtubules. Only in animal cells! Not

necessary for spindle formation.



Attachment point on Chromatids for

spindle fiber



The portion of the mitotic spindle that is

connected to the chromosome during

mitosis



The microtubules that are responsible for

separating as well as pushing centrosomes towards the opposite

ends of the cells.



Microtubules of the mitotic spindle that

are not connected to chromosomes but are

responsible for pushing centrosomes

apart.


• Centromere• Centrosome• Centriole• Kinetochore• Kinetochore microtubules• Mitotic spindle• Nonkinetochore microtubules• Spindle apparatus• Spindle fibers The mitotic spindle as

visible through a light microscope.



Bundles of microtubules that

comprise the spindle apparatus. This bundling is what

allows us to visualize the fibers through a

light microscope

Phases of the Cell Cycle (Eukaryotes)

• Interphase (not mitosis)

• Mitosis– Prophase– Prometaphase– Metaphase– Anaphase– Telophase– Cytokinesis


• Interphase• Mitosis is the shortest

part of the cell cycle.• Interphase accounts

for about 90% of the cell cycle.

• Cells:– Grow– Copy chromosomes– Prepare for cell

division


• Interphase is divided into subphases:– G1 Phase = Gap 1

– S Phase = synthesis

– G2 Phase = Gap 2

• During all three subphases, the cell grows by producing proteins and organelles.

Figure 12.5 The stages of mitotic cell division: interphase

Late interphase

Nucleus is well defined and bounded by the nuclear envelope

Duplicated chromosomes are loosely packed chromatin fibers

Microtubules extend from the duplicated centrosomes

Figure 12.5 The stages of mitotic cell division: prophase

Prophase: 1st Phase of Mitosis

Nucleoli disappear

Chromatin fibers become tightly coiled in the nucleus condensing into discrete chromosomes

Centrosomes move away from each other as mitotic spindle begins to form in the cytoplasm

Figure 12.5 The stages of mitotic cell division: prometaphase

Prometaphase

Nuclear envelope fragments

Chromosomes condense further and form kinetochores (structures at the centromere region that microtubules bind)

Microtubules extend from each pole and invade the nuclear area and either attach to kinetochores or microtubules from the opposite side

Figure 12.5 The stages of mitotic cell division : metaphase

Metaphase

Centrisome are at opposite poles

Chromosomes line up at the center of the cell equidistant from each pole (metaphase plate)

Microtubules are attached to the kinetochores of each sister chromatid facing its pole

Figure 12.5 The stages of mitotic cell division : anaphase

Anaphase

Paired centromeres of each chromosome separate, dividing the sister chromatids

Centrosome poles move farther apart

Microtubules begin to shorten, pulling their attached chromosome towards opposite poles

Figure 12.5 The stages of mitotic cell division : telophase and cytokinesis

Telophase

Daughter nuclei form at the two poles

Nuclear envelopes begin to form from the fragments of the parent cell

Chromatin fibers loosen

Cytokinesis

A cleavage furrow forms between daughter cells and the cell is pinched in two, equally dividing the cytoplasm

Figure 12.5x Mitosis

Prometaphase

The Mitotic Spindle: A Closer Look

• The mitotic spindle– Is an apparatus of

microtubules that controls chromosome movement during mitosis

• The spindle arises from the centrosomes– And includes spindle

microtubules and asters

• Some spindle microtubules– Attach to the

kinetochores of chromosomes and move the chromosomes to the metaphase plate

CentrosomeAster

Sisterchromatids

MetaphasePlate

Kinetochores

Overlappingnonkinetochoremicrotubules

Kinetochores microtubules

Centrosome

ChromosomesMicrotubules0.5 µm

1 µm

Figure 12.7

Separating Chromosomes

• During anaphase, sister chromatids are separated– Proteins that hold the chromatids together are

inactivated– Kinetochores have motor proteins that move the

chromosomes along microtubules towards the spindle poles

• Nonkinetochore microtubules elongate the cell

Figure 12.7 Testing a hypothesis for chromosome migration during anaphase

Model:

Chromosomes travel along microtubules towards the poles

Microtubules shorten by depolymerizing at their

kinetochore ends

Experiment:

Microtubules of dividing cells are labeled with a fluorescent dye

A laser bleaches the dye in a region midway between one

spindle pole and the chromosome

As chromosomes move towards the poles, microtubules on the kinetochore side of the mark shortened, while those on the centrosome side remained the

same length

Cytokinesis : division of cytoplasm

• Animal cells : cleavage– Cleavage furrow

• Division begin as a shallow groove in the cell surface near the metaphase plate

– Contractile ring (on the cytoplasmic side of the furrow)• Composes of actin microfilaments and the protein myosin

– Cleavage furrow deepens until the parent cell is pinched in two

• Plant cells : cell plate formation– Vesicles from the Golgi collect at the middle of the cell

producing a cell plate– Cell wall material carried in the vesicles is deposited on

the plate as it grows, until it fuses with the membrane along the perimeter of the cell

Figure 12.8 Cytokinesis in animal and plant cells

Figure 12.9 Mitosis in a plant cell

Spindle forms

Nuclear envelope fragments

Microtubules capture kinetochores

Chromosomes line up at metaphase plate

Chromatids separate and move towards

poles

Cell plate forms

Chromatin condensing

• Cell division by binary fission

• Bacterial chromosome is a single circle of DNA

• Replication of DNA begins at a specific origin of replication

• Duplicated chromosomes actively move apart without the help of mitotic spindle

Evolution of Mitosis: prokaryotic reproduction

Figure 12.10 Bacterial cell division (binary fission)

Figure 12.11 A hypothesis for the evolution of mitosis

Mitotic spindle form outside of the nucleus

Nuclear envelope breaks down

Microtubules separate the chromosomes

Mitotic spindle form in the nucleus

Nuclear envelope remains intact

Microtubules separate the chromosomes

Microtubules pass through the nucleus in cytoplasmic tunnels

Nuclear envelope remains intact

Chromosomes attach to envelope

Chromosomes move to opposite ends of the cell by unknown mechanisms

Protists: Plankton

Algae: Phytoplankton

Cell Cycle Regulation

• Timing and rate of cell division is critical for normal growth, development, and maintenance– Skin cells divide frequently– Liver cells divide only when needed (repair)– Muscle cells and nerve cells do not divide

• Molecular mechanisms regulate the cell cycle• Improper cell cycle regulation can result in human

disease : cancer

Evidence for Cytoplasmic Signals• Molecules present in the cytoplasm

– Regulate progress through the cell cycleIn each experiment, cultured mammalian cells at two different phases of the cell cycle were induced to fuse.

When a cell in the M phase was fused with a cell in G1, the G1 cell immediately began mitosis— a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

EXPERIMENTS

RESULTS

CONCLUSION The results of fusing cells at two different phases of the cell cycle suggest that molecules present in the cytoplasm of cells in the S or M phase control the progression of phases.

When a cell in the S phase was fused with a cell in G1, the G1 cellimmediately entered the S phase—DNA was synthesized.

S

S S M M

MG1 G1

Experiment 1 Experiment 2

Figure 12.13 A, B

Figure 12.13 Mechanical analogy for the cell cycle control system

The cell cycle is regulated at certain checkpoints by both internal and external controls

Checkpoints• Critical regulatory points where activating and

inhibiting signals can control progression through the cell cycle– Stop signals predominant at checkpoints until overridden

by an activating signal• Signals come from cell surveillance mechanisms

– Informing the cell when all processes in the current phase have been completed correctly or not

• Signals come from outside the cell• Checkpoints

– G1 phase : restriction point• cells that do not pass this point go into a nondividing G0 phase

– G2 phase– M phase

Cell Cycle Control Molecules

• The fluctuation in the amount and activity of regulatory molecules in the cytoplasm pace the sequential events of the cell cycle

• Kinases that drive the cell cycle - Cdks (cyclin dependent kinases)

– Present at a constant concentration in an inactive form

– Activated by attachment to a cyclin

• Activity of Cdks rises and falls with changes in the concentration of its cyclin partner

Figure 12.14 Molecular control of the cell cycle at the G2 checkpoint

• MPF = M phase (maturation) Promoting Factor– triggers the passage

past the G2 checkpoint into M phase by phosphorylating proteins involved in nuclear envelope breakdown

– Initiates process leading to the destruction of its cyclin, switching itself off and driving the cell past the M phase checkpoint

Cdk + cyclin combine to form MPF

MPF causes the

breakdown of cyclin

MPF promotes mitosis

Signals that Regulate the Cell Cycle

• Internal signals– M phase checkpoint: anaphase does not

begin until all chromosomes are attached to spindle on the metaphase plate

– Kinetochores not attached to spindle send a signal to delay anaphase

• External signals– Growth factors (eg: PDGF)– Density-dependent inhibition of cell division

Figure 12.15 The effect of a growth factor on cell division

Platelet-derived growth factor (PDGF) stimulates the division of human

fibroblast cells

Figure 12.15x Fibroblast growth

Figure 12.16 Density-dependent inhibition of cell division

Density-dependent inhibition:

A cell population reaches a certain density, growth

factors and nutrients available to each cell

becomes insufficient to allow continued cell

growth

Anchorage dependence:

Cells must be attached to a substratum to divide – signals are transmitted to cell cycle control via

plasma membrane proteins and elements of the cytoskeleton linked

to them

Cancer• Cancer cells do not respond to normal cell cycle controls

and divide excessively– Make a required growth factor themselves– Abnormal cell cycle control system– Abnormality in signaling pathway that conveys the growth factor

signal• Cancer cells divide indefinitely if supplied with nutrients: in

vitro cell lines (HeLa cells)• Transformation – the process that converts a normal cell

to a cancer cell• Tumor – a mass of abnormal cells that have evaded the

immune system– Benign: cell mass remains at original site– Malignant: tumor invades organs and impairs function

• Metastasis – spread of cancer cells to locations distant from the original site– cancer cells can lose attachments to other cells and spread into

nearby tissues or enter the blood stream.

Figure 12.17 The growth and metastasis of a malignant breast tumor

Homework• Text:

– Pg. 234: Self Quiz 1 - 11 (due 2/6/12)

chapter 12: cell cycle. chromosome sorting the goal of cell division typically is to equally...

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