AP Biology

Ch. 7 – The Cell Cycle and Cell Division

Originally prepared by Kim B. Foglia Revised and adapted by Nhan A. Pham

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-  growth (from fertilized egg to multicellular organisms)

Why do cells divide?

amoeba

http://www.youtube.com/watch?v=qvuvqNATZA8

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-  reproduction (asexual reproduction, unicellular organisms)

-  repair and renewal (replace cells that die from normal wear and tear or from injury)

Why do cells divide?

amoeba

http://www.youtube.com/watch?v=QDdVs4qM1XU

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Getting the right stuff §  What is passed on to daughter cells? -  exact copy of chromosomes -  organelles, cytoplasm, cell membrane, enzymes (in

cytokinesis)

chromosomes (stained orange) in kangaroo rat epithelial cell → notice cytoskeleton fibers

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The Cell Cycle

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Cell cycle M

Mitosis

G1Gap 1

G0Resting

G2Gap 2

SSynthesis

§  Cell has a “life cycle”

cell is formed from a mitotic division

cell grows & matures to divide again

cell grows & matures to NEVER divide again

G1, S, G2, M G1→ G0

epithelial cells, blood cells, stem cells

liver cells

brain/nerve cells, muscle cells

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Interphase §  Divided into 3 phases §  G1 (1st Gap) -  cell doing its “everyday job” -  grows

§  S (Synthesis of DNA) -  copies chromosomes

§ G2 (2nd Gap) -  prepares for division -  cell grows (more) -  produces organelles,

proteins, membranes

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§  dividing cell replicates DNA

§  human cell duplicates ~2 meters of DNA

§  error rate ~1 per 100 million bases

§  3 billion base pairs in mammalian genome (~30 errors per cell cycle)

§  mutations (to somatic (body) cells)

S phase: Replicating DNA M

Mitosis

G1Gap 1

G0Resting

G2Gap 2

SSynthesis

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Organizing DNA §  DNA is organized in

chromosomes

§  double helix DNA molecule

§  wrapped around histone proteins

§  chromatin is DNA-protein complex, organized into long thin fiber condensed further during mitosis

DNA

histones

chromatin

duplicated mitotic chromosome

ACTGGTCAGGCAATGTC

double stranded chromosome

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Mitotic Chromosome §  2 sister chromatids §  held together by adhesive

proteins at centromeres §  contain identical

copies of original DNA

homologous chromosomes

homologous chromosomes

sister chromatids homologous = “same information” single-stranded double-stranded

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§  Chromatin condenses to form visible chromosomes §  Centrioles move to opposite poles of cell

§  Protein fibers cross cell to form mitotic spindle

§  Nucleolus disappears

§  Nuclear membrane breaks down

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§  spindle fibers attach to centromeres, creating kinetochores

§  microtubules attach at kinetochores

§  connect centromeres to centrioles

§  chromosomes begin moving

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§  Chromosomes align along middle of cell (metaphase plate)

§  spindle fibers coordinate movement, ensuring chromosomes separate properly so each new nucleus receives only 1 copy of each chromosome

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§  sister chromatids separate at kinetochores, moving to opposite poles

§  pulled at centromeres by motor proteins “walking”along microtubules

§  process powered by ATP §  poles move farther apart

§  polar microtubules lengthen

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Separation of Chromatids §  In anaphase, proteins holding together sister chromatids

are inactivated §  sister chromatids separate to become individual

chromosomes

2 chromosomes 1 chromosome 2 chromatids single-stranded

double-stranded

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§  Kinetochores use motor proteins that “walk” chromosome along attached microtubule

§  microtubule shortens by dismantling at kinetochore (chromosome) end

Chromosome Movement

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§  chromosomes arrive at opposite poles

§  daughter nuclei form

§  chromosomes disperse and no longer visible under light microscope

§  Spindle fibers disperse

§  cytokinesis begins with cleavage furrow forming

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Cytokinesis in Animals

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Mitosis in whitefish blastula

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Mitosis in animal cells

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Cytokinesis in Plants §  cell plate forms

§  Golgi-derived vesicles line up at equator

§  vesicles fuse to form 2 cell membranes

§  new cell wall laid down between membranes

§  new cell wall fuses with existing cell wall

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Cytokinesis in plant cell

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Mitosis in Plant Cell

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Origin of replication

chromosome: double-stranded

DNA replication

of DNA

elongation of cell

cell pinches in two

ring of proteins

Evolution of Mitosis §  Mitosis in

eukaryotes likely evolved from binary fission in bacteria

§  single circular chromosome

§  no membrane-bound organelles

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The Cell Cycle Control System §  The sequential events of the cell cycle are directed by a

distinct cell cycle control system, which is similar to a clock

Control system

G2 checkpoint

M checkpoint

G1 checkpoint

G1

S

G2 M

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§  G1 is a key period

in cell control

§  cell must grow to a certain size during G1 before DNA synthesis (cytoplasmic volume-to-genome size ratio)

§  restriction point is point of no return

G1 checkpoint

G1

G1

G0

(a) If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

(b) If a cell does not receive a go-ahead signal at the G1checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.

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The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases (CDK) §  Two types of regulatory proteins are involved in cell cycle

control §  Cyclins (an M-phase promoting factor or “MPF”) and

cyclin-dependent kinases (Cdks)

Bovine cyclin A

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§  The activity of cyclins and Cdks fluctuates during the cell cycle

During G1, conditions in the cell favor degradation of cyclin, and the Cdk component of MPF is recycled.

5

During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G1 phase.

4

Accumulated cyclin molecules combine with recycled Cdk mol- ecules, producing enough molecules of MPF to pass the G2 checkpoint and initiate the events of mitosis.

2

Synthesis of cyclin begins in late S phase and continues through G2. Because cyclin is protected from degradation during this stage, it accumulates.

1

Cdk

Cdk G2 checkpoint

Cyclin MPF

Cyclin is degraded

Degraded Cyclin

G1 G1 S G2 G2 S M M MPF activity

Cyclin

Time

(a) Flucation of MPF activity and cyclin concentration during the cell cycle

(b) Molecular mechanisms that help regulate the cell cycle

MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase.

3 Figure 12.16 A, B

M

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Growth Factors §  Growth factors stimulate other cells to divide

EXPERIMENT

A sample of connective tissue was cut up into small pieces.

Enzymes were used to digest the extracellular matrix, resulting in a suspension of free fibroblast cells.

Cells were transferred to sterile culture vessels containing a basic growth medium consisting of glucose, amino acids, salts, and antibiotics (as a precaution against bacterial growth). PDGF was added to half the vessels. The culture vessels were incubated at 37°C.

3

2

1 Petri plate

Without PDGF

With PDGF

Scalpels

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§  In density-dependent inhibition, crowded cells stop dividing

§  Most animal cells exhibit anchorage dependence (they must be attached to a substratum to divide)

Cells anchor to dish surface and divide (anchorage dependence).

When cells have formed a complete single layer, they stop dividing (density-dependent inhibition).

If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition).

Normal mammalian cells. The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer.

(a)

25 µm

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Cancer Cells §  exhibit neither density-dependent inhibition nor

anchorage dependence

§  do not respond to control mechanisms

§  form tumors

http://www.youtube.com/watch?v=Y2kTEbyMvXA

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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.

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

3 A tumor grows from a single cancer cell.

1

Tumor

Glandular tissue Cancer cell

Blood vessel

Lymph vessel

Metastatic Tumor