Ch 12 The Cell Cycle Interphase M phase

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Ch. 12 The Cell Cycle • Interphase • M phase INTERPHASE – Mitosis –

Ch. 12 The Cell Cycle • Interphase • M phase INTERPHASE – Mitosis – Cytokinesis S (DNA synthesis) C E TI S O A IT H M ) P (M C M yto ito ki si ne s si s G 1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 2

Cell Division - Purpose Reproduction – unicellular organisms – binary fission in bacteria Growth

Cell Division - Purpose Reproduction – unicellular organisms – binary fission in bacteria Growth & development from fertilized egg Repair (& replacement) of damaged cells 100 µm (a) Reproduction. An amoeba, a single-celled eukaryote, is dividing into two cells. Each new cell will be an individual organism (LM). 200 µm 20 µm (b) Growth and development. (c) Tissue renewal. These dividing This micrograph shows a bone marrow cells (arrow) will sand dollar embryo shortly after give rise to new blood cells (LM). the fertilized egg divided, forming two cells (LM). Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Figure 12. 4 Chromosome duplication and distribution during cell division 0. 5 µm A

Figure 12. 4 Chromosome duplication and distribution during cell division 0. 5 µm A eukaryotic cell has multiple chromosomes, one of which is represented here. Before duplication, each chromosome has a single DNA molecule. Once duplicated, a chromosome consists of two sister chromatids connected at the centromere. Each chromatid contains a copy of the DNA molecule. Mechanical processes separate the sister chromatids into two chromosomes and distribute them to two daughter cells. Chromosome duplication (including DNA synthesis) Centromere Separation of sister chromatids Centrometers Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Sister chromatids

Figure 12. 5 The cell cycle INTERPHASE 90% of cell’s life 5 -6 hrs.

Figure 12. 5 The cell cycle INTERPHASE 90% of cell’s life 5 -6 hrs. 10 -12 hrs. S (DNA synthesis) G 1 C E TI S O A IT PH ) (M M C M yto ito ki si ne s si s growth 1 hr. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 2 growth 4 -6 hrs.

INTERPHASE An organism’s genome: - Total genes in the cell of a species -

INTERPHASE An organism’s genome: - Total genes in the cell of a species - Nuclear & extra-nuclear (mito & chloro) G 1 Human chromosome number: - - 2 n - diploid s 46 – somatic cell (body cells) C M yto ito ki si ne s si - G 2 23 – gamete (sex cells – sperm & egg) n - haploid (M C E TI S O A IT PH ) M - Chromosomes: - Chromatin - DNA & proteins Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings S (DNA synthesis)

Interphase Centromsomes – with 2 centrioles Nucleus – with mass of chromatin Nucleolus in

Interphase Centromsomes – with 2 centrioles Nucleus – with mass of chromatin Nucleolus in nucleus Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Phases of Mitosis INTERPHASE • Prophase Prometaphase – chromosomes are S in Pairs G

Phases of Mitosis INTERPHASE • Prophase Prometaphase – chromosomes are S in Pairs G (DNA synthesis) 1 • Metaphase – chromosomes in Middle C M yto ito ki si ne s si s • Anaphase – chromosomes Apart (M C E TI S O A IT PH ) M • Telophase – Two cells Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 2

Figure 12. 6 Exploring The Mitotic Division of an Animal Cell G 2 OF

Figure 12. 6 Exploring The Mitotic Division of an Animal Cell G 2 OF INTERPHASE Centrosomes (with centriole pairs) Nucleolus Chromatin (duplicated) Nuclear Plasma envelope membrane PROPHASE Early mitotic spindle Aster Centromere Chromosome, consisting of two sister chromatids Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PROMETAPHASE Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule

Figure 12. 6 Exploring The Mitotic Division of an Animal Cell METAPHASE ANAPHASE Metaphase

Figure 12. 6 Exploring The Mitotic Division of an Animal Cell METAPHASE ANAPHASE Metaphase plate Spindle Centrosome at Daughter one spindle pole chromosomes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings TELOPHASE AND CYTOKINESIS Cleavage furrow Nuclear envelope forming Nucleolus forming

Cytokinesis: • division of the cytoplasm • animal cells – Forms cleavage furrow •

Cytokinesis: • division of the cytoplasm • animal cells – Forms cleavage furrow • plant cells – Forms a cell plate Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Figure 12. 9 Cytokinesis in animal and plant cells Cleavage furrow Contractile ring of

Figure 12. 9 Cytokinesis in animal and plant cells Cleavage furrow Contractile ring of microfilaments 100 µm Vesicles forming cell plate Wall of patent cell 1 µm Cell plate New cell wall Daughter cells (a) Cleavage of an animal cell (SEM) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings (b) Cell plate formation in a plant cell (SEM)

Molecular Control of Cell Cycle • regulated at checkpoints • kinases - cyclin-dependent kinase

Molecular Control of Cell Cycle • regulated at checkpoints • kinases - cyclin-dependent kinase (CDK) • cyclins G 1 checkpoint - MPF - maturation promoting factor - Cyclin + CDK = MPF Control system S G 1 - (mitosis promoting factor) M M checkpoint Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 2 checkpoint – cyclin dependent complex CDK complex (go ahead signal)

Figure 12. 15 The G 1 checkpoint G 0 G 1 checkpoint G 1

Figure 12. 15 The G 1 checkpoint G 0 G 1 checkpoint G 1 (a) If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 1 (b) If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state.

(a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Relative Concentration

(a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Relative Concentration Figure 12. 16 Molecular control of the cell cycle at the G 2 checkpoint G 1 S G 2 M MPF activity G 1 S G 2 M Cyclin MPF – maturation promoting factor Time (b) Molecular mechanisms that help regulate the cell cycle 1 Synthesis of cyclin begins in late S phase and continues through G 2. Because cyclin is protected from degradation during this stage, it accumulates. 5 During G 1, conditions in S G 1 the cell favor degradation of cyclin, and the Cdk component of MPF is recycled. Cdk Cyclin is degraded 4 During anaphase, the cyclin component of MPF is degraded, terminating the M phase. The cell enters the G 1 phase. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings G 2 M Degraded Cyclin G 2 Cdk checkpoint MPF Cyclin 2 Accumulated cyclin molecules combine with recycled Cdk molecules, producing enough molecules of MPF to pass the G 2 checkpoint and initiate the events of mitosis. 3 MPF promotes mitosis by phosphorylating various proteins. MPF‘s activity peaks during metaphase. (breaking down nuclear envelop, etc. )

Control of Cell Cycle • Cyclin accumulates - late S phase – Binds to/activating

Control of Cell Cycle • Cyclin accumulates - late S phase – Binds to/activating CDK • Producing MPF • MPF at G 2 initiates mitosis • Anaphase - cyclin component of MPF degrades • M phase terminates - cell -> G 1 Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Kinetochore microtubules shorten at their kinetochore ends CONCLUSION This experiment demonstrated that during anaphase,

Kinetochore microtubules shorten at their kinetochore ends CONCLUSION This experiment demonstrated that during anaphase, kinetochore microtubules shorten at their kinetochore ends, not at their spindle pole ends. This is just one of the experiments supporting the hypothesis that during anaphase, a chromosome tracks along a microtubule as the microtubule depolymerizes at its kinetochore end, releasing tubulin subunits Chromosome movement Microtubule Kinetochore Tubulin subunits Motor protein Chromosome Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Prophase: • chromatin - condenses • nucleoli disappear. • sister chromatids appear • mitotic

Prophase: • chromatin - condenses • nucleoli disappear. • sister chromatids appear • mitotic spindle forms • centrosomes move away from each other Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Prometaphase: • nuclear envelope fragments • microtubules join chromosomes • 2 chromatids/chromosome – kinetochore

Prometaphase: • nuclear envelope fragments • microtubules join chromosomes • 2 chromatids/chromosome – kinetochore center • “kinetochore microtubules. ” - jerk the chromosomes back and forth. • Nonkinetochore microtubules interact with opposite poles Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Metaphase: • Metaphase - longest stage – about 20 min. • centrosomes at opposite

Metaphase: • Metaphase - longest stage – about 20 min. • centrosomes at opposite ends. • chromosomes convene on metaphase plate, – at centromeres • Sister chromatid kinetochores – attached to kinetochore microtubules • spindle - apparatus of microtubules Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Anaphase: • shortest stage - a few minutes. • 2 sister chromatids part –

Anaphase: • shortest stage - a few minutes. • 2 sister chromatids part – chromatid becomes chromosome • move toward opposite ends of the cell, – kinetochore microtubules shorten • cell elongates – nonkinetochore microtubules lengthen • finally the ends have equivalent—complete— collections of chromosomes Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Telophase: • 2 daughter nuclei form • Nuclear envelopes form • chromosomes -less condensed

Telophase: • 2 daughter nuclei form • Nuclear envelopes form • chromosomes -less condensed • Mitosis – the division of 1 nucleus into 2 genetically identical nuclei - complete Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Figure 12. 7 The mitotic spindle at metaphase Aster Sister chromatids Centrosome Metaphase Plate

Figure 12. 7 The mitotic spindle at metaphase Aster Sister chromatids Centrosome Metaphase Plate Kinetochores Overlapping nonkinetochore microtubules Kinetochores microtubules 0. 5 µm Microtubules Chromosomes Centrosome 1 µm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Lack of Cell Cyle Controls - Cancer Cells Figure 12. 18 Density-dependent inhibition and

Lack of Cell Cyle Controls - Cancer Cells Figure 12. 18 Density-dependent inhibition and anchorage dependence of cell division (a) Normal mammalian cells. The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer. 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). 25 µm (b) Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells. Cancer cells do not exhibit anchorage dependence or density-dependent inhibition. 25 µm Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Figure 12. 19 The growth and metastasis of a malignant breast tumor Lymph vessel

Figure 12. 19 The growth and metastasis of a malignant breast tumor Lymph vessel Tumor Blood vessel Glandular tissue 1 A tumor grows from a single cancer cell. 2 Cancer cells invade neighboring tissue. Cancer cell 3 Cancer cells spread through lymph and blood vessels to other parts of the body. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Metastatic Tumor 4 A small percentage of cancer cells may survive and establish a new tumor in another part of the body.

Lab: Figure 12. 10 Mitosis in a plant cell Chromatine Nucleus Nucleolus condensing 1

Lab: Figure 12. 10 Mitosis in a plant cell Chromatine Nucleus Nucleolus condensing 1 Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is staring to from. Chromosome Metaphase. The 2 Prometaphase. 3 4 spindle is complete, We now see discrete and the chromosomes, chromosomes; each attached to microtubules consists of two at their kinetochores, identical sister are all at the metaphase chromatids. Later plate. in prometaphase, the nuclear envelop will fragment. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 5 Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of cell as their kinetochore microtubles shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divided the cytoplasm in two, is growing toward the perimeter of the parent cell.

Plant Cells – meristematic tissue (root tip) Copyright © 2005 Pearson Education, Inc. publishing

Plant Cells – meristematic tissue (root tip) Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Bacterial cell division (binary fission) Origin of replication Cell wall E. coli cell 1

Bacterial cell division (binary fission) Origin of replication Cell wall E. coli cell 1 Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. 2 Replication continues. One copy of the origin is now at each end of the cell. 3 Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. 4 Two daughter cells result. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Two copies of origin Origin Plasma Membrane Bacterial Chromosome Origin