Transcript Cell Cycle and Review of Basic Genetics

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 fertilization
3A3: 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
G1
S
(DNA synthesis)
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
G1 checkpoint
• Checkpoints are regulated by internal and external
signals
G1
• 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
Control
system
M
G2
M checkpoint
G2 checkpoint
S
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
G0
G1 checkpoint
G1
(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
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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
G2
M
G1
S
G2
M
G1
MPF activity
Cyclin
concentration
Time
(a) Fluctuation of MPF activity and cyclin concentration during
the cell cycle
Degraded
cyclin
G2
checkpoint
Cyclin is
degraded
MPF
Cdk
Cyclin
(b) Molecular mechanisms that help regulate the cell cycle
Cyclin accumulation
Cdk
Degraded
cyclin
G2
checkpoint
Cyclin is
degraded
MPF
Cdk
Cyclin
(b) Molecular mechanisms that help regulate the cell cycle
Cyclin accumulation
Cdk
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
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
25 µm
25 µm
(a) Normal mammalian cells
(b) Cancer cells
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-hbosimmortal-life-of-henrietta-lacks-film-adaptation-true-blood-execproducer-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
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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.
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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.
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Reproduction issues
• Civic issues such as ownership of genetic information, privacy, historical contexts, etc.