Cell Cycle and Review of Basic Genetics

3A2: In eukaryotes, heritable information is passed to the next generations via processes that include the cell cycle and

mitosis or meiosis plus fertilization3A3: The chromosomal basis of inheritance provides an

understanding of the pattern of passage (transmission) of genes from parent to offspring

Main Ideas of This Week•Cycle Cycle•Regulation of cell cycle via chemicals• Internal and external signals that influence cell cycle

•Cancer: when cell cycle is broken•Mitosis vs Meiosis•Basics of Mendelian genetics

Cell Cycle• Cell cycle: life of a cell from the time it is first

formed from a diving parent cell until its own division into two cells

• Phases of the Cell Cycle: • Mitotic (M) Phase: includes mitosis

(division of DNA) and cytokinesis (division of cytoplasm)

• Interphase: accounts for about 90% of the cycle; during this phase the cell grows and copies chromosomes to prepare for mitosis; divided into three sub-phases (during all three phases the cell grows by producing proteins and cytoplasmic organelles such as mitochondrian and endoplasmic reticulum

• G1 Phase: first gap; growth• G2 Phase: second gap; growth• S Phase: synthesis; DNA is duplicated

S(DNA synthesis)

MITOTIC(M) PHASE

Mito

sis

Cytokinesis

G1

G2

Pair Share•Discuss with your partner…what is the difference between Interphase and Mitosis.

•What are the three sub-phases of Interphase? What is happening during each phase?

•What are the phases of Mitosis? Does anyone remember I passed my algebra test??????

Cell Cycle Control System• Cell cycle is a complex set of stages that is regulated by

checkpoints; determine the ultimate fate of the cell; controlled by the cycling of sets of molecules that trigger and coordinate events in cycle

• Checkpoints are regulated by internal and external signals

• Checkpoint: a control point where stop and go-ahead signals can regulate the cycle (signals are transmitted by signal transduction pathways!!! – yes those wonderful pathways we started to learn about last week…)

• Animal cells have mechanisms that prevent the cell cycle from going further unless crucial processes have occurred; once the processes have occurred they provide a signal for the cell to continue onto the next phase of the cell cycle

• There are three major checkpoints in the cell cycle: G1 checkpoint, G2 checkpoint, and M checkpoint

SG1

M checkpoint

G2M

Controlsystem

G1 checkpoint

G2 checkpoint

More details about Checkpoints• G1 checkpoint seems to be the most important; if cell receives a go-ahead signal at the G1

checkpoint it will usually complete G1, S, G2 and M phases and divide• If the cell does not receive the go-ahead signal it will exit the cycle and switch into an

nondividing state called the G0 phase• Most cells in the human body are in the G0 phase (mature nerve cells, muscles cells)• Other cells, such as liver cells can be “called back” from the G0 phase to the cell cycle by

external cues, such as growth factors released during injury

G1

G0G1 checkpoint

(a) Cell receives a go-ahead signal

G1(b) Cell does not receive a go-ahead signal

The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases

• Two regulatory proteins contro cell cycling: cyclins and cyclin-dependnet kinases (Cdks)• Remember protein kinases activate or inactivate other proteins by phosphorylation• Specific protein kinases give the go-ahead signals at the G1 and G2 checkpoints• Many of the kinases that drive the cell cycle are present at a constant concentration;

most of the time the enzyme is in the inactive form (turned off)• Kinase become active when it binds/attaches to a cyclin• MPF: “maturation-promoting factor” aka “M-phase-promoting factor” refers to the

complex of a Cdk+cyclin

Fig. 12-17

M G1 S G2M G1 S G2 M G1

MPF activity

Cyclinconcentration

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

Degradedcyclin

Cdk

G 1S

G 2

M

CdkG2checkpointCyclin is

degraded

CyclinMPF

(b) Molecular mechanisms that help regulate the cell cycle

Cyclin accumulation

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

2. Accumulated cyclin molecule combine with recycled Cdk molecules, producing enough molecules of MPF for the cell to pass the G2 checkpoint and initiate the events of mitosis

3. MRP promotes mitosis by phosphorylating various proteins. MPF’s activity peaks during metaphase

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

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

Cyclin isdegraded

Cdk

MPF

Cdk

M

S

G 1

G2checkpoint

Degradedcyclin

Cyclin

(b) Molecular mechanisms that help regulate the cell cycle

G2

Cyclin accumulation

1

23

4

5

Debrief/Process• What are the two regulatory proteins of the cell cycle?• When the two regulatory proteins of the cell cycle bind

together what is the complex called?• Explain how the cycling on these molecules controls the

cell cycle• Explain the role checkpoints play in the cell cycle• What is G0 phase? Why types of cells enter G0?

Internal and external signals provide stop-and-go signs at checkpoints• Internal Chemical Factors:

• fluctuation in chemicals (mitosis-promoting factors)• External Chemical Factors:

• Cells fail to divide if an essential nutrients is lacking in the culture medium; even if all other conditions are favorable some will not divide unless a specific growth factor (protein released by certain cells that stimulate other cells to divide) is present; researchers have found over 50 different growth factors; different cell types respond specifically to different growth factors or combinations of growth factors

• Ex: Without PDGF (a type of human growth factor) fibroblasts (a type of connective tissue cell) will not divide

• Fibroblasts have PDGF receptors on their plasma membranes, binding of PDGF molecules to the receptors (which happen to be receptor tyrosine kinases) triggers a signal transduction pathway that allows the cell to pass the G1 checkpoint and divide

• When injury of fibroblast occurs in the body platelets release PDGF in the area to promote fibroblast cell division

External Physical Factors • Density-dependent inhibition: crowded cells stop dividing;

cultured cells normally divide until they form a single layer of cells on the inner surface of the culture container, if some cells are removed, cells boarding the open space will begin to divide again until the space is filled

• Ex: of cell-cell communication; binding of a cell-surface protein to its counterpart on an adjoining cell sends a growth-inhibiting signal to both cells; preventing them from moving forward in the cell cycle

• Anchorage dependence: to divide cells must be attached to a surface

Anchorage dependence

Density-dependent inhibition

Density-dependent inhibition

(a) Normal mammalian cells (b) Cancer cells25 µm25 µm

Loss of Cell Cycle Controls in Cancer Cells• Cancer cells do not follow normal signals that regulate the cell cycle;

they divide excessively and invade other tissues; if unchecked they can kill the organism

• Cancer cells do not stop dividing when growth factors are depleted; thought that cancer cells may make their own growth factors OR have an abnormality in the cell cycle control system that allows them to continue to divide in the absence of the factors

• Cancer cells can go on dividing indefinitely in culture if they are given a continual supply of nutrients; they are basically “immortal”

Pair Share• Have you ever heard of Henrietta Lack? Or HeLa cells?• As we are studying the cell cycle there are still many unanswered

questions about how the cell cycle works. If you were to go into the hospital for a procedure and the doctors removed tissues from your body to do research would this be an ethical practice? Why or why not?

• If there was a discovery found as a result of your tissues from your body should you be compensated? Should you be notified?

• How would you feel if your tissue was associate with a major medical discovery? Say your tissue happened to CURE cancer. Are there any issues you could predict as a result of your tissues being involved in the discovery?

Video Links• https://www.youtube.com/watch?v=0gF8bCE4wqA

• http://blogs.indiewire.com/shadowandact/movement-on-hbos-immortal-life-of-henrietta-lacks-film-adaptation-true-blood-exec-producer-will-pen-script

• https://www.youtube.com/watch?v=rlINobLQvlg

• https://www.youtube.com/watch?v=y38pgPY6Zq0

Review of types of cells• Somatic cells: all cells in the body except for reproductive cells

• Remember these cells are diploid (2N=46 in humans) • Divide via Mitosis – results in two identical diploid cells that contain the same DNA

as the parent cell• Asexual reproduction: 1 parent produces identical cell

• Sex cells: spermatogonia (located in testes) and oogonia (located in ovaries)• These cells start as diploid cells (2N=46 in humans)• Divide via Meiosis – results in four unique halpoid reproductive cells (gametes:

sperm or egg) that contains 50% of the parent cells DNA• Sexual reproduction: sperm (N) and egg (N) join together (2 parents) to produce a

unique diploid organism (2) through the process of fertilization

Mitosis• Mitosis passes a complete genome from the parent cell to daughter

cells. • Mitosis occurs after DNA replication.• Mitosis followed by cytokinesis produces two genetically identical daughter

cells.• Mitosis plays a role in growth, repair, and asexual reproduction.• Mitosis is a continuous process with observable structural features along the

mitotic process. Evidence of student learning is demonstrated by knowing the order of the processes (replication, alignment, separation).

Meiosis• Meiosis, a reduction division, followed by fertilization ensures genetic diversity in

sexually reproducing organisms.• Meiosis ensures that each gamete receives one complete haploid (n) set of chromosomes. • During meiosis, homologous chromosomes are paired, with one homologous chromosomes

are paired, with one homologue originating from the maternal parent and the other from the paternal parent. Orientation of the chromosome pairs is random with respect to the cell poles.

• Separation of the homologous chromosomes ensures that each gamete receives a haploid (n) set of chromosomes composed of both maternal and paternal chromosomes.

• During meiosis, homologous chromatids exchange genetic material via a process called “crossing-over,” which increases genetic variation in the resultant gametes.

• Fertilization involves the fusion of two gametes, increases genetic variation in populations by providing for new combinations of genetic information in the zygote, and restores the diploid number of chromosomes.

Mendelian Genetics• Essential knowledge 3A3: The chromosomal basis of inheritance provides an understanding of the pattern of passage (transmission) of

genes from parent to offspring.• Rules of probability can be applied to analyze passage of single gene traits from parent to offspring.• Segregation and independent assortment of chromosomes result in genetic variation

• Segregation and independent assortment can be applied to genes that are on different chromosomes.• Genes that are adjacent and close to each other on the same chromosome tend to move as a unit; the probability that they will segregate as a unit is a

function of the distance between them.• The pattern of inheritance (monohybrid, dihybrid, sex-linked, and genes linked on the same homologous chromosome) can often be predicted from data

that gives the parent genotype/phenotype and/or the offspring phenotypes/genotypes.

• Certain human genetic disorders cab be attributed to the inheritance of single gene traits or specific chromosomal changes, such as nondisjunction.

• Sickle cell anemia• Tay-Sachs disease• Huntington’s disease• X-linked color blindness• Trisomy 21/Down syndrome• Klinefelter’s syndrome

• Many ethical, social and medical issues surround human genetic disorders.• Reproduction issues

• Civic issues such as ownership of genetic information, privacy, historical contexts, etc.