The Cell Cycle Chapter 8

1
The Cell Cycle Chapter 8

• Individual cells reproduce. This is true of both
  prokaryotic eukaryotic cells, animals,
  plants, simple and complex.
• To reproduce, a cell divides into 2 daughter
  cells, both equal in all respects.
• In order to divide, the cell must first make
  enough materials (replicate things) so
• each daughter cell will have them.
• In multicellular organisms, each individual
• cell is in one stage or another of the cell
• division process, and if a picture is made,
• various stages will be seen (such as in
• the onion tip sample below)
• Cell cycle (This term is
• only applied to eukaryotic
• cells) The series of stages
• that result in 2 daughter
• cells, starting with just one.
• - Within the cell cycle, there
• are stages, or times, at
• which the cell is either
• resting, or making various
• types of changes to the whole

Bacteria E. coli
Human cell
2
The cell cycle in Eukaryotes

• Unicellular Eukaryotes -
• - Cells divide to produce 2 identical organisms.
• Multi-cellular Eukaryotes (animals and plants)
  The cell cycle is very similar in all types of
  eukaryotes (processes, proteins, etc.)
• - Usually develop from a single original cell,
  called a fertilized egg. This cell will later
  divide, and the resulting cells will also divide
  many times, ending in the entire animal or plant.
  
• - Thus, in cell divisions occur in 2 different
  life processes
• 1) reproduction when reproductive cells are
  made (eggs, sperm)
• 2) growth cells divide so that a small
  organism becomes larger (this has nothing to
  do with production or more individuals.
• - Plants Specialized root cells divide into
  cells that will become other parts of the plant
  (branches, leaves, etc.)
• - Animals Like in plants, different types of
  cells will be produced from division of the
  original ones, and will become different parts of
  the animal.
• - (Both). The timing, and the amount of cell
  divisions are coordinated
• - Different types of tissues divide at
  different speeds
• - Some tissues divide more (continue to growth)
  more than others.
• - Communication among cells allows regulation
  of growth (division)

3
Phases of the Eukaryotic cell cycle

• Every cell completes the cell cycle, ending in
  cell division (2 daughter cells). At each cell,
  by the end of the cycle 2 things will have
  happened
• 1- Mitosis- individual chromosomes are sorted
  and distributed to each daughter cell. Begins
  with breaking of nucleus membrane
• 2- Cytokinesis the original cell
• becomes 2 cells.
• The period between divisions is called
  Interphase. Individual chromosomes are not
  visible in the nucleus (they have not
  condensed). So, interphase is the longest of
  the 5 phases of the cell cycle, including
• G1, (GO), S, and G2

• The cell cycle includes 5 phases, and each
• cell is always in one of them
• 1- G1 (Gap 1 or prereplication)
• 2- go to GO (non-dividing cells) or go to
• 3- S (DNA synthesis)
• 4- G2 (Gap 2 or premitosis)
• 5- M (Mitosis)

4
The Gap phases G1 (G0), G2

• The Gap phases G1 and G2.
• - Cells grow and synthesize RNA, proteins and
  other macromolecules
• - Cells either do the function they are supposed
  to do in their tissue/organ, or, they go on to
  the next S or M phases of the cell cycle.
• - Different cells spend very different amounts
  of time in each phase, depending on the type of
  tissue they belong to.
• G1 phase Begins when a cell is first formed, as
  soon as is a separate cell. The cell can either
  continue on to the next phase of the cell cycle,
  or stop in G0. G0 is a stopping point within G1.
• - Most cells in adult multicellular organisms
  are in G0.
• - Cells in G0 are metabolically active, doing
  their function within a tissue/organ.

Cells in G1 phase may receive a signal to
continue on to the next phases (S, M), or to stop
at G0. The Restriction Point (R) is a point of
no return If the cell passes R, it cant go
back or stop, it will just go on to S and M and a
new cell cycle begins.
5
Leaving G0 and going or not !

• Cells from different tissues/organs vary greatly
  in whether they remain in G0 or continue past R
  (Restriction Point), to S and M phases.
• - Cells that have a short life-span need to be
  replaced quickly, so they spend little time in G0
  (stem cells in bone marrow tissue need to replace
  erythrocytes with only 120 days of life)
• - Cells with long life-spans (liver cells) are
  in G0 most or all the time. The organ itself
  (liver) doesnt grow more once the organism is an
  adult. The cells will only go on to division
  cycles (the rest of the cell cycle) if they need
  to be replaced due to surgery, wounds, etc.
• - Brain and other neural cells are always in G0
  and normally dont go thru cell division.
  Therefore, mature nerve cells cant be
  regenerated.

6
G0 to S phase.and then G2 and M

• S phase If a cell passes G0, it goes into S
  phase, and continues thru the rest of the cell
  cycle.
• - S stands for synthesis (additional DNA is
  synthesized, so there will be enough for 2 cells,
  each receiving a complete copy of the genetic
  information)
• - S includes DNA replication (mechanism for
  making more DNA Each chromosome makes an
  identical copy of itself, resulting in 2
  identical sets of chromosomes). Thus, the number
  of genes in the nucleus is exactly doubled.
• - DNA replication involves DNA polymerase (and
  enzyme).
• G2 phase From S, cells go to G2, where the cell
  prepares for mitosis.
• - G2 stands for growth and metabolism
• - Specific types of RNA and proteins and
  synthesized, that will have a role during Mitosis
  (M)
• M phase (Mitosis) The chromosomes are visible
  through light microscopes (During interphase the
  preceeding steps, G1, G0, S the chromosomes
  filled the nucleus and are spread out and not
  clearly visible.
• - Sometimes called Nuclear Division (begins with
  1 nucleus, and ends with 2)
• - Divisions take place to ensure each cell will
  receive a copy of each chromosome (there are 4
  stages of divisionsee later)
• - After mitosis, the whole cell (including
  external plasma membrane) divides in 2 cells ?
  Cytokinesis. After that, each daughter cell
  enters G1 again.

7
DNA structure
Antiparallel

• After mitosis, each daughter cell ends with a
  complete set of chromosomes that are of the same
  type and number as the parent cell.
• Remember the specific pairs
• Adenine pairs only with Thymine
• ( they form 2 hydrogen bonds)
• Cytosine pairs only with Guanine
• (they form 3 hydrogen bonds)
• The 2 strands of DNA (sugar-phosphate backbones)
  run in opposite directions (see ring sugars
  upside down on left strand). This arrangement is
  called Antiparallel structure of DNA.

8
DNA synthesis

• DNA replication has 3 main steps
• 1- Binding of enzymes to existing DNA
• - Occurs at sites called replication origins
  (several in eukaryotes, only one in prokaryotes)
• - A replisome is formed (combination of DNA
  polymerase, and RNA-synthetizing enzyme, and
  other enzymes).
• 2- Un-winding of the double helix
• - Replisomes move away from the replication
  origin, and into the old double strand,
  splitting it (this is the unwinding process)
• 3- Synthesis of a new matching strand for each
  existing strand.
• - An enzyme makes short sections of RNA that
  will serve as primer, made according to the
  nitrogen bases present in the old strands.
• - DNA polymerase adds nucleotides at the end of
  the strand only.
• - On the leading strand, DNA polymerase adds
  nucleotides at the end of the RNA primer.
• - Another enzyme replaces the small RNA primer
  with DNA.

lagging
leading
Replisomes Moving and splitting
9
DNA synthesis (cont.)

• Synthesis is continuous in the leading strand,
  and discontinuous in the lagging strand. In the
  lagging strand, it occurs in short, unconnected
  segments, because the replisome is moving in the
  opposite direction.
• 2 identical strands of DNA result from the old
  one, so there are 2 chromosomes in place of each
  original one.
• DNA replication is semi-conservative
  (half-conservative), because each new DNA has one
  side from the old strand.
• The structure of DNA is only seen at mitosis. At
  interphase, DNA and proteins are loose masses in
  the nucleus.
• Nucleosomes are the basic packing unit of
  eukaryotic chromosomes. They are like protein
  spools or cores, attached to one another.
• Histone proteins have a controlling role in DNA
  synthesis. They bind to DNA and turn-off
  synthesis by excluding the enzymes involved in
  gene expression. Histones must be modified for
  synthesis to occur..

10
Chromosome structure

• DNA is bound in nucleosomes as Chromatin
  (uncondensed conformation, where individual
  chromosomes can not be clearly seen). This is the
  form DNA occurs most of the time in eukaryotic
  cells (G1, G0).
• Chromosomes are seen clearly as thread-like
  bodies only during preparation for cell division.
• Histones attach to nucleosomes making the DNA
  inactive.
• Enzymes can modify the histones attached to
  genes, loosening the chromatin structure and
  activating the DNA. This activation occurs during
  the S-phase of the cell cycle.
• This mechanism allows organisms to have different
  cell types with some active groups of genes and
  some silent genes at the same time.

11
DNA repair

• Mutation Any change in the sequence of a cells
  DNA. They are mistakes. Those that persist to
  the next cell division will be inherited. Three
  types
• - Non-harmful (silent) - Harmful -Lethal to the
  cells.
• Cells have methods for correcting errors in DNA
  replication, and to repair damage to DNA
  resulting from mutagenic chemicals or radiation.
  2 examples
• 1- DNA polymerase proof-reads its work by
  checking each base pair after adding a new
  nucleotide to a new chain. If incorrect, it
  removes it and replaces it with the right one.
• 2- Excision repairs (cut-out and replace damaged
  sections) A mismatch of bases is recognized by
  an enzyme which binds to the site, breaks the
  sugar-phosphate strand and removes the damaged
  portion. DNA polymerase synthesizes a short
  patch. A third enzyme repairs the sugar-phosphate
  strand.
• The frequency of mutations by DNA polymerase
  errors is low 1/10 million base pairs.

12
Stages of cell division

• During the S phase of the cell cycle, each
  chromosome is replicated, resulting in 2 copies
  called sister chromatids. They remain attached by
  a centromere.
• During the M phase (mitosis), sister chromatids
  will separate (chromosome segregation). The
  nucleus of each of the 2 daughter cells receives
  one of each chromosomes.
• If due to an error, a nucleus does not receive a
  copy of a chromosome (the other nucleus receives
  both), the resulting cells are called aneuploid
  cells (incorrect numbers of chromosomes).

centromere
chromatid
Human chromosomes arranged as homologous pairs
(most eukaryotes are diploidhave 2 copies of
each chromosome). Thus, during replication, 4
copies of each chromosome will be seen. Human
somatic cells have 23 pairs, including one pair
of sex chromosomes, which In males (above) is
XY, and in females is XX.
13
Mitosis A continuous process with 4 stages
Profase Nuclear membrane breaks, chromosomes
become visible. Microtubules begin to form,
joining into a Mitotic Spindle
Interphase In animal cells, centrioles are
duplicated.
Inter-Pro- Meta- Ana- Telo-
Anaphase Sister chromatids separate, and are
moved by motor proteins towards opposite spindle
poles.
Metaphasechromosomes arranged in the metaphase
plate between the 2 poles of the cell,
perpendicular to the spindle. Sister chromatids
remain attached.
Anaphase (cont.) Separated sister chromatids are
now chromosomes.
Telophase nuclear membranes are formed around
each group of chromosomes, making 2 nuclei.
Plasma membrane begins to constrict by
cytokinesis.
14
Mitosis (some names we must know)

• Structure description
  formed during plants animals
• Mitotic spindle System of microtubules
  Prophase yes yes
• Duplicated centrioles Unclear role
  Interphase no
  yes
• Spindle poles Each end of the cell, join
  Prophase no yes
• microtubules to centrioles
• Kinetochores Protein complex in each
  Prophase no yes
• centriole
• Tubulin protein that makes up the
• microtubules in the spindle Pro-
  to anaphase yes yes
• GTP (Guanosine E-rich molecule like ATP
  Pro- to anaphase yes yes
• triphosphate) for making
  microtubules
• Motor proteins Proteins in kinetochores,
  pull Meta to anaphase yes yes
• chromosomes into position
• Cell plate (made of Beginning of a cell
  wall late telophase yes
  no
• vacuoles between daughter cells
• Aneuploid cells daughter cells
  receiving
• incorrect s of chromosomes all
  Mitosis yes yes

15
Mitosis in easier diagrams (animal)
Prophase (early)
Prophase (mid)
Prophase (late)
Metaphase
Interphase
Telophase
Anaphase (early)
Anaphase (late)

• Interphase- nuclear membrane well defined.
  Nucleolus visible in nucleus. Chromosomes not
  visible.
• Prophase- (early) centrioles begin to move
  apart. Chromosomes appear as long threads.
• (middle) centrioles farther apart, sister
  chromatids visible. (late) centrioles at
  opposite ends Spindle connects centromeres to
  opposite poles of spindle nuclear membrane
  dissappearing.
• Metaphase- Nuclear membrane gone kinetochore
  microtubules move sister chromatids to the
  metaphase plate (middle)
• Anaphase- (early) centromeres have split and
  chromosomes have began moving apart. (late) sets
  of chromosomes nearing theirn respective poles.
  Cytokinesis begins.
• Telophase- new nuclear membranes are formed.
  Nucleolus reappears. Chromosomes become longer,
  thinner, less distinct. Cytokinesis nearly
  complete.

16
Cytokinesis

• Sometimes described as an step within telophase.
  It actually can be seen as beginning earlier, in
  late anaphase. Regardless, telophase ends with
  the formation of 2 nuclei. Then cytokinesis will
  be completed.
• In algal cells, a pinching of the cell membrane
  occurs from the outside towards the interior, and
  then the cell wall breaks.
• In Plants, vacuoles are formed from the inside,
  forming a cell plate. Then complete separation
  will occur.

17
Evolution of Mitosis

• In Prokaryotes there is no nucleus the nucleoid
  is attached to the plasma membrane. Division will
  occur in about the same manner as in eukaryotes.
• In primitive Eukaryotes, the chromosomes attach
  to the nuclear membrane, and the nuclear membrane
  never breaks down, but together with
  microtubules, serves to give physical support.
• In some dinoflagellates (types of algae),
  microtubules go thru either parallel of multiple
  holes in the nuclear membrane.
• In more advanced Eukaryotic cells (including
  plants and animals), the nuclear membrane breaks
  down, microtubules in the spindle hold and
  separate chromosomes during stages of mitosis,
  and then the new nuclear membranes are formed.

dinoflagellates
Primitive Eukaryotes nuclear membrane
never breaks down during mitosis
Advanced Eukaryotes including plants and animals
18
Practice !! (make sure you know why)
19
Practice !! (make sure you know why)
Early Telophase, Begin cytokinesis
Interphase
Early prophase
Early Anaphase
Metaphase
Late Prophase
Late telophase, Advanced cytokinesis
Mid- Prophase
Late Anaphase
20
(No Transcript)
21
Control of the cell cycle

• Cyclin proteins regulate the timing and
  progression of the cell cycle. The mechanisms are
  very similar in all types of eukaryotic cells,
  from simple yeasts, to humans.
• - G1 cyclins begin to accumulate in late G1
  phase and peak during S phase.
• - Mitotic cyclins accumulate in late S phase
  (when DNA synthesis is completed), and peak at
  metaphase. Then they begin to dissapear.
• Kinases Enzymes that transfer a phosphate group
  from ATP to other enzymes, to make them active.
• Cyclins bind to kinases. Kinases are present thru
  the cell cycle but are only active when cyclins
  are bound to the appropriate cyclin.
• Through the cell cycle, the levels of specific
  cyclins change, activating or deactivating
  certain kinases. The activated kinases in turn
  activate enzymes needed during the various steps
  of the cell cycle.

22
Some cyclinkinase dependent processes

• - In prophase the nuclear membrane breaks
  down.During G2, when mitotic kinases begin to
  accumulate, phosphate groups are added by
  kinases to enzymes involved in breaking the
  membrane.
• - More kinases are activated to mediate the
  condensation of chromosomes, and yet others are
  activated for the spindle to be made.
• - The breaking down of each specific type of
  cyclins is mediated by the same type of
  mechanisms at the end of each phase of the cell
  cycle. Thus, mitotic cyclins end their own
  activity at the end of mitosis, to ensure the
  cell goes on to the next phase of the cell cycle
  (G1).

23
Checkpoints

• Many things can go wrong during the cell cycle
• - Various types of aneuploidy
• - Damage to DNA
• - Improper formation of mitotic spindle
• Ckeckpoint controls monitor the condition of
  key factors/processes, protecting the organisms
  from uncontrolled/incorrect growth of damaged
  cells.
• Cell-cycle arrest When the cell stops at a
  particular place of the cell cycle, so repairs
  can be made to damages of various types. The
  arrest is caused by proteins that detect problems
  (mistakes, damage), and halt to cycle.
• - P53 (human protein that detects mismatched
  base pairs). P53 activates inhibitors that
  prevent the G1 cyclin-kinases to make the cell
  proceed from G1 into S. The repair is made (thru
  excision repairs), and P53 becomes inactive
  again.
• - Checkpoints ensure that problems are corrected
  before the cycle progresses further.
• - Mutations in genes that encode for proteins
  involved in regulation of the cell cycle may
  cause cells to divide at the wrong time or
  uncontrollably. Some cancers appear to be
  related to this type of problems.

24
Cancer
- Tumor Mass of cells that divides
uncontrollably due to problems with checkpoint
control mechanisms. - Metastasis of tumor cells
break off and travel to other parts of the body.

• - Proto-oncogenes- genes involved in promoting
  cell division
• - Tumor suppressors- genes involved in
  inhibiting cell division
• Mutations in proto-oncogenes can convert them to
  oncogenes (cancer genes) that stimulate cells to
  leave G0 and divide, whether or not there is an
  external signal to do so. Thus oncogenes override
  checkpoint control mechanisms.
• Mutations in tumor suppressors can make them
  inactive and thus unable to control formation of
  tumors.
• In many cancer cells, mutations have occurred in
  both proto-oncogenes and tumor-suppressor genes.

25
More practice!
26
(No Transcript)
27
(No Transcript)
28
(No Transcript)