1. Overview: The Key Roles of Cell Division The ability of organisms to reproduce best distinguishes living things from nonliving matter (reproduction is an emergent property of life) The continuity of life is based on the reproduction of cells, or cell division Cell Theory: all cells come from pre-existing cells

2. Division in unicellular vs multicellular organisms In unicellular organisms, standard cell division of one cell reproduces the entire organism Multicellular organisms depend on standard cell division only for: – Development from a fertilized cell – Growth – Repair Not for reproducing the entire organism

3. Cell division is carefully controlled in all normal cells In eukaryotes division is a part of the cell cycle-a programmed series of events that governs the life of a cell

4. Concept 12.1: Cell division results in genetically identical daughter cells Standard cell division results in daughter cells with “identical” genetic information and DNA -clones -vegetative reproduction -asexual reproduction A special type of division produces nonidentical daughter cells for reproduction of the organism (gametes, or sperm and egg cells) - sexual reproduction

5. All the DNA in a cell constitutes the cell’s genome (nuclear genome, organelle genome) A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells) DNA molecules in a eukaryotic cell are packaged into organelles called chromosomes Genetic material must be duplicated and separated to produce clones

6. The number of chromosomes is characteristic for each species “n” Gametes (reproductive cells: sperm and eggs) contain n chromosomes Somatic cells (nonreproductive cells) have two sets of chromosomes or 2n (2n = 46 for humans) Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein

7. In preparation for cell division, DNA is copied or “replicated”. A somatic cell temporarily has 2 x 2n chromosomes Genetic material must be duplicated to produce clones

8. DNA molecules are many times longer than their cells. The chromatin that contains this DNA must be tightly packed for travel to daughter cells. Chromatin “packing” is called condensation Genetic material must be separated to produce clones

9. Packing Ratio 10,000-100,000 X

10. Packed and duplicated chromosomes each have two sister chromatids The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached The centromere defines two “arms” (p and q) for each chromatid The end of the chromatid is the telomere Structural features of chromosomes

11. Concept 12.2: The active division phase alternates with non-division in the cell cycle In the 1800’s the active division phase was named “mitosis” and the non-dividing phase named “interphase” The two terms have been adapted for modern usage to describe the cell cycle The modern cell cycle consists of mitosis and cytokinesis – Mitotic (M) phase (mitosis and cytokinesis)- nuclear and cytoplasmic division – Interphase (cell growth and copying of chromosomes in preparation for cell division)

12. Interphase (about 90% of the time of the cell cycle) can be subdivided further: – G 1 phase (“first gap”) – S phase (“synthesis”) – G 2 phase (“second gap”) The cell grows during all three phases, but chromosomes are duplicated only during the S phase

13. Eukaryotic Cell Cycle S (DNA synthesis) MITOTIC (M) PHASE Mitosis Cytokinesis G1G1 G2G2

14. Mitosis is conventionally subdivided into five parts: – Prophase – Prometaphase – Metaphase – Anaphase – Telophase Cytokinesis overlaps telophase

15. PrometaphaseProphase G 2 of Interphase Nonkinetochore microtubules Fragments of nuclear envelope Aster Centromere Early mitotic spindle Chromatin (duplicated) Centrosomes (with centriole pairs) Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore microtubule Prophase-the cell prepares to divide: chromosome condensation begins, Spindle starts to assemble Prometaphase-preparation continues: final condensation, spindle finishes, nuclear membrane fragments

16. MetaphaseAnaphase Telophase and Cytokinesis Cleavage furrow Nucleolus forming Metaphase plate Centrosome at one spindle pole Spindle Daughter chromosomes Nuclear envelope forming Metaphase-chromosomes line up at the middle of the cell Anaphase-sister chromatids separate to form new “daughter” chromosomes, pulled to opposite spindle poles Telophase- daughter cells reorganize, reverse of prophase

17. Prophase Fig. 12-6a Prometaphase G 2 of Interphase

18. Fig. 12-6c MetaphaseAnaphase Telophase and Cytokinesis

19. The Mitotic Spindle The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis During prophase, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them

20. During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes Different microtubules overlap with microtubules coming from the other centrosome (spindle pole).

21. Cytokinesis In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow In plant cells, a cell plate forms during cytokinesis

22. Cleavage furrow 100 µm Contractile ring of microfilaments Daughter cells (a) Cleavage of an animal cell (SEM)(b) Cell plate formation in a plant cell (TEM) Vesicles forming cell plate Wall of parent cell Cell plate Daughter cells New cell wall 1 µm

23. Binary Fission Prokaryotes (bacteria and archaea) reproduce by a simpler type of cell division called binary fission In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart

24. Fig. 12-11-4 Origin of replication Two copies of origin E. coli cell Bacterial chromosome Plasma membrane Cell wall Origin

25. Concept 12.3: The eukaryotic cell cycle is regulated by a molecular control system The frequency of cell division varies with the type of cell These cell cycle differences result from regulation at the molecular level

26. Evidence for Cytoplasmic Signals The cell cycle appears to be driven by specific chemical signals present in the cytoplasm Some evidence for this hypothesis comes from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei

27. Experiment 1 Experiment 2 EXPERIMENT RESULTS SG1G1 M G1G1 M M S S When a cell in the S phase was fused with a cell in G 1, the G 1 nucleus immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G 1, the G 1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

28. The sequential events of the cell cycle are directed by a cytoplasmic factors The cycle has specific checkpoints where the it stops until a go-ahead signal is received Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) The cell makes Cdks continuously but cyclins only when needed for division The activity of cyclins and Cdks fluctuates during the cell cycle-they serve as go-ahead signal at checkpoints

29. Fig. 12-14 S G1G1 M checkpoint G2G2 M Control system G 1 checkpoint G 2 checkpoint

30. Cyclin is degraded Cdk MPF Cdk M S G1G1 G 2 checkpoint Degraded cyclin Cyclin G2G2 Cyclin accumulation

31. An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide

32. Loss of Cell Cycle Controls in Cancer Cells Cancer cells do not respond normally to the body’s control mechanisms Cancer cells may not need growth factors to grow and divide: – They may make their own growth factor – They may convey a growth factor’s signal without the presence of the growth factor – They may have an abnormal cell cycle control system

33. A normal cell is converted to a cancerous cell by a process called transformation Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue If abnormal cells remain at the original site, the lump is called a benign tumor Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors

34. Multistep Model for Cancer Tumor suppressors hold back cancer, oncogenes are genes that are capable of initiating cancer Mutant oncogenes or tumor suppressor genes can be inherited

35. Environmental factors can trigger cancer Carcinogens are chemicals that lead to cancer Proto-oncogenes mutate to become fully active oncogenes Above shows several ways that proto-oncogenes can mutate

36. Viruses can trigger cancer Virus genes can remain in cells and act as oncogenes (v-oncogenes) Virus genes can remain in cell and activate cellular oncogenes (c- oncogenes) Cancer viruses, tumor viruses or oncoviruses

37. Example Mutations can lead to altered function at any step

38. Environmental factors, genetic factors, viruses can trigger cancer They act through a multi-step model to de- regulate cell division They work through genes called oncogenes

39. NOTE CARD QUESTION DISTINGUISH BETWEEN: TUMOR SUPPRESSOR/ONCOGENE V-ONCOGENE/C-ONCOGENE