CONCEPT 12.1: Most cell division results in genetically identical daughter cells • The ability of organisms to produce more of their own kind is the one characteristic that distinguishes living things from nonliving matter • The continuity of life is based on the reproduction of cells, or cell division
Key Roles of Cell Division • Cell division plays several important roles in life • Single-celled organisms give rise to new organisms through cell division • Multicellular eukaryotes undergo embryonic development through cell division • Cell division continues to function in renewal and repair in fully grown multicellular eukaryotes
• A crucial function of most cell division is the distribution of identical genetic material to the two daughter cells • Cell division is remarkably accurate in passing DNA from one generation to the next
Cellular Organization of the Genetic Material • All the DNA in a cell constitutes the cell’s 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 cell are packaged into chromosomes • The DNA molecule of a chromosome carries several hundred to a few thousand genes
• Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division • Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus • Somatic cells (nonreproductive cells) have two sets of chromosomes • Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells
Distribution of Chromosomes During Eukaryotic Cell Division • In preparation for cell division, DNA is replicated and the chromosomes condense • Each duplicated chromosome has two sister chromatids (joined copies of the original chromosome), attached along their lengths by cohesins • The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached
• During cell division, the two sister chromatids of each duplicated chromosome separate and move into two nuclei • Once separate, the chromatids are called chromosomes
• Eukaryotic cell division consists of – mitosis, the division of the genetic material in the nucleus – cytokinesis, the division of the cytoplasm • Gametes are produced by a variation of cell division called meiosis • Meiosis yields nonidentical daughter cells that have half as many chromosomes as the parent cell
CONCEPT 12.2: The mitotic phase alternates with interphase in the cell cycle • In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis • During the period between one cell division and the next, many critical events occur
Phases of the Cell Cycle • The cell cycle consists of – mitotic (M) phase (mitosis and cytokinesis) – interphase (cell growth and copying of chromosomes in preparation for cell division)
• Interphase (about 90% of the cell cycle) can be divided into three phases: – 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
The Mitotic Spindle: A Closer Look • The mitotic spindle is a structure made of microtubules that controls chromosome movement during mitosis • In animal cells, assembly of spindle microtubules begins in the centrosome, a type of microtubule- organizing center • The centrosome replicates during interphase, forming two centrosomes that migrate to opposite ends of the cell during prophase and prometaphase
• By the end of prometaphase, the two centrosomes are at opposite end of the cell • An aster (a radial array of short microtubules) extends from each centrosome • The spindle includes the centrosomes, the spindle microtubules, and the asters
• Each sister chromatid has a kinetochore • A kinetochore is a protein complex associated with centromeres • During prometaphase, some spindle microtubules (kinetochore microtubules) attach to the kinetochores • At metaphase, the chromosomes are all lined up at the metaphase plate, an imaginary plane midway between the spindle’s two poles
• In anaphase, the cohesins are cleaved by an enzyme called separase • Sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell • The microtubules shorten by depolymerizing at their kinetochore ends
• Results of a clever experiment suggest that motor proteins on kinetochores “walk” the chromosomes along the microtubules during anaphase • The depolymerization of the microtubules at the kinetochore ends occurs after the motor proteins have passed • This is called the “Pac-man” mechanism
• Other research shows that chromosomes are “reeled in” by motor proteins at the spindle poles • Microtubules depolymerize after they pass by the motor proteins at the poles • The general consensus is that both mechanisms are used
• Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell • At the end of anaphase, duplicate groups of chromosomes have arrived at opposite ends of the elongated cell • Cytokinesis begins during anaphase or telophase, and the spindle eventually disassembles
Cytokinesis: A Closer Look • In animal cells, cytokinesis occurs by a process known as cleavage • The first sign of cleavage is the appearance of a cleavage furrow, a shallow groove in the cell surface near the old metaphase plate • In plant cells, a cell plate forms during cytokinesis
Binary Fission in Bacteria • Prokaryotes (bacteria and archaea) reproduce by a 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 • The plasma membrane pinches inward, dividing the cell into two • How bacterial chromosomes move and their location established are active areas of research
The Evolution of Mitosis • Because prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission • Certain unicellular eukaryotes exhibit types of cell division that seem intermediate between binary fission and mitosis
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 differences result from regulation at the molecular level • Cancer cells manage to escape the usual controls on the cell cycle
The Cell Cycle Control System • The cell cycle appears to be driven by specific signaling molecules 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 • Signals in the cytoplasm of the fused cell caused both nuclei to enter the same phase of the cell cycle
• The sequential events of the cell cycle are directed by a distinct cell cycle control system • The cell cycle control system is regulated by both internal and external controls • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received
The Cell Cycle Clock: Cyclins and Cyclin- Dependent Kinases • Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclin-dependent kinases (Cdks) • Cyclins are named for their cyclically fluctuating concentrations in the cell • The activity of a Cdk rises and falls with changes in concentration of its cyclin partner • Cdks must be attached to a cyclin to be active
• MPF (maturation-promoting factor) is a cyclin-Cdk complex that triggers a cell’s passage past the G 2 checkpoint into the M phase • Peaks of MPF activity correspond to the peaks of cyclin concentration • MPF acts both as a kinase and indirectly through activating other kinases
Stop and Go Signs: Internal and External Signals at the Checkpoints • Many signals registered at checkpoints come from cellular surveillance mechanisms within the cell • Checkpoints also register signals from outside the cell • Three important checkpoints are those in the G 1, G2, and M phases
• For many cells, the G1 checkpoint seems to be the most important • If a cell receives a go-ahead signal at the G 1 checkpoint, it will usually complete the S, G 2, and M phases and divide • If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase
• An example of an internal signal is that cells will not begin anaphase until all chromosomes are properly attached to the spindle at the metaphase plate • This mechanism ensures that daughter cells have the correct number of chromosomes
• External factors, both chemical and physical influence cell division • Growth factors are released by certain cells and stimulate other cells to divide • Platelet-derived growth factor (PDGF) is made by blood cell fragments called platelets • PDGF is required for the division of cultured fibroblasts
• In density-dependent inhibition, crowded cells will stop dividing • Most animal cells also exhibit anchorage dependence—to divide, they must be attached to a substratum • Density-dependent inhibition and anchorage dependence check the growth of cells at an optimal density • Cancer cells exhibit neither type of regulation of their division
Loss of Cell Cycle Controls in Cancer Cells • Cancer cells do not heed the normal signals that regulate the cell cycle • They do not stop dividing when growth factors are depleted • Cancer cells do 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
• Cells that acquire the ability to divide indefinitely have undergone transformation • Cancer cells that are not eliminated by the immune system form tumors, masses of abnormal cells within otherwise normal tissue • If abnormal cells remain only at the original site, the lump is called a benign tumor • Most benign tumors do not cause serious problems (depending on their location)
• Malignant tumors invade surrounding tissues and can undergo metastasis, the spread of cancer cells to other parts of the body, where they may form additional tumors • Localized tumors may be treated with high-energy radiation, which damages the DNA in the cancer cells • The majority of cancer cells have lost the ability to repair DNA damage
• Metastatic tumors are treated with chemotherapeutic drugs that target the cell cycle • Side effects of chemotherapy are due to the effects of the drugs on normal cells that divide frequently • Researchers are producing a flood of information about cell-signaling pathways and their relationship to cancer • Coupled with new molecular techniques, treatments for cancer are becoming more “personalized” to a particular patient’s tumor