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

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

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

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

Genetic material must be duplicated and separated to produce clones 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

The number of chromosomes is characteristic for each species 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

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

Genetic material must be separated to produce clones 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

Packing Ratio 10,000-100,000 X

Structural features of chromosomes 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

The modern cell cycle consists of 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 Mitotic (M) phase (mitosis and cytokinesis)- nuclear and cytoplasmic division Interphase (cell growth and copying of chromosomes in preparation for cell division)

Interphase (about 90% of the time of the cell cycle) can be subdivided further: G1 phase (“first gap”) S phase (“synthesis”) G2 phase (“second gap”) The cell grows during all three phases, but chromosomes are duplicated only during the S phase

S (DNA synthesis) G1 Cytokinesis G2 Mitosis Eukaryotic Cell Cycle INTERPHASE S (DNA synthesis) G1 Cytokinesis G2 Mitosis Figure 12.5 The cell cycle MITOTIC (M) PHASE

Mitosis is conventionally subdivided into four parts: Prophase Metaphase Anaphase Telophase Cytokinesis overlaps telophase For the Cell Biology Video Myosin and Cytokinesis, go to Animation and Video Files.

Chromosome, consisting of two sister chromatids Prophase-the cell prepares to divide: chromosome condensation begins, Spindle starts to assemble G2 of Interphase Prophase Prometaphase Centrosomes (with centriole pairs) Chromatin (duplicated) Early mitotic spindle Aster Centromere Fragments of nuclear envelope Nonkinetochore microtubules Figure 12.6 The mitotic division of an animal cell Nucleolus Nuclear envelope Plasma membrane Chromosome, consisting of two sister chromatids Kinetochore Kinetochore microtubule Prometaphase-preparation continues: final condensation, spindle finishes, nuclear membrane fragments

Telophase and Cytokinesis Metaphase-chromosomes line up at the middle of the cell Anaphase-sister chromatids separate to form new “daughter” chromosomes, pulled to opposite spindle poles Metaphase Anaphase Telophase and Cytokinesis Metaphase plate Cleavage furrow Nucleolus forming Figure 12.6 The mitotic division of an animal cell Daughter chromosomes Nuclear envelope forming Spindle Centrosome at one spindle pole Telophase- daughter cells reorganize, reverse of prophase

G2 of Interphase Prophase Prometaphase Fig. 12-6a Figure 12.6 The mitotic division of an animal cell G2 of Interphase Prophase Prometaphase

Telophase and Cytokinesis Fig. 12-6c Figure 12.6 The mitotic division of an animal cell Metaphase Anaphase Telophase and Cytokinesis

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 For the Cell Biology Video Spindle Formation During Mitosis, go to Animation and Video Files.

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).

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

Figure 12.9 Cytokinesis in animal and plant cells Vesicles forming cell plate Wall of parent cell 1 µm 100 µm Cleavage furrow Cell plate New cell wall Figure 12.9 Cytokinesis in animal and plant cells Contractile ring of microfilaments Daughter cells Daughter cells (a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)

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

Cell wall Origin of replication Plasma membrane E. coli cell Bacterial Fig. 12-11-4 Cell wall Origin of replication Plasma membrane E. coli cell Bacterial chromosome Two copies of origin Origin Origin Figure 12.11 Bacterial cell division by binary fission

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

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

EXPERIMENT RESULTS Experiment 1 Experiment 2 S G1 M G1 S S M M When a cell in the S phase was fused with a cell in G1, the G1 nucleus immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G1, the G1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Figure 12.13 Do molecular signals in the cytoplasm regulate the cell cycle?

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

G1 checkpoint Control system S G1 G2 M M checkpoint G2 checkpoint Fig. 12-14 G1 checkpoint Control system S G1 G2 M Figure 12.14 Mechanical analogy for the cell cycle control system M checkpoint G2 checkpoint

G1 S Cyclin accumulation Cdk M Degraded G2 cyclin G2 Cdk checkpoint Figure 12.17 Molecular control of the cell cycle at the G2 checkpoint Cyclin is degraded Cyclin MPF

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

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

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

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

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

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

Example Mutations can lead to altered function at any step

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