The Cell Cycle

Interphase
G1 Phase-cell growth (2n l-shaped)
S Phase-copying chromosomes in prep. For Mitosis (2n x-
shaped)
G2 Phase-More cell growth and prep for mitosis
Mitosis (M Phase)
Prophase-mitotic spindles form (centrioles in animal cells only)
and attach to spindle at kinetochore (centromere and
corresponding DNA Segment)
Metaphase-chromosomes migrate to middle of cell (metaphase
plate)
Anaphase-kinetochore microtubules shorten, pulling
chromosomes
Telophase-accompanies cytokinesis (2 daughter nuclei, each is
2n l-shaped)
Cytokinesis-clevage furrow forms as actin and myosin
contract in a ring around the elongated cell in animal cells.
In plants, a cell plate forms between the daughter cells,
dividing them (results in 2 cells
Figure 11-3
Unreplicated chromosome
The unreplicated chromosome consists of
a single, long strand of DNA wrapped
around proteins (proteins not shown).

Gene 1 Gene 2

The DNA replicates,

resulting in two copies of
the same chromosome..
Replicated
chromosome Gene 1 Gene 2
Copies of same
chromosome Gene 1 Gene 2

The DNA condenses

around its associated
proteins, resulting in a
compact chromosome
that is 10,000 times shorter
than its original length.

Condensed
replicated
chromosome
Copies of same
chromosome,
condensed Centromere
Figure 11-5
Mitosis

G2 DIVISION

G1

INTERPHASE
Figure 11-7a-1

PRIOR TO MITOSIS
Chromosomes replicate.

Centrosomes Chromosomes

Centrioles

1. Interphase: After chromosome

replication, each chromosome is
composed of two sister chromatids.
Centrosomes have replicated.
Figure 11-7a-2

MITOSIS
Sister chromatids separate; one chromosome copy goes to each daughter nucleus.

Early mitotic spindle Kinetochore

Spindle
fibers

2. Prophase: Chromosomes 3. Prometaphase: Nuclear 4. Metaphase:

condense, and mitotic spindle envelope breaks down. Chromosomes complete
begins to form. Spindle fibers contact migration to middle of cell.
chromosomes at kinetochore.
Figure 11-7b

CYTOKINESIS
Cytoplasm
is divided.

5. Anaphase: Sister chromatids 6. Telophase: The nuclear 7. Cell division begins: Actin- 8. Cell division is
separate. Chromosomes are envelope re-forms, and the myosin ring causes the plasma complete: Two
pulled to opposite poles of the cell. spindle apparatus disintegrates. membrane to begin pinching in. daughter cells form.
Figure 11-7b-1

5. Anaphase: Sister chromatids 6. Telophase: The nuclear

separate. Chromosomes are envelope re-forms, and the
pulled to opposite poles of the cell. spindle apparatus disintegrates.
Binary Fission
Bacterial Cell Division
In stead of centrioles, chromosome is
attached to and remains attached to the
plasma membrane
The bacterial cell elongates, separating
the chromosome and its copy
When the growth and separation are
complete, cytokinesis occurs
Figure 11-8
STEPS IN BACTERIAL CELL DIVISION

1. Chromosome 2. Chromosome 3. Chromosomes 4. FtsZ ring 5. Fission

is located mid- replicates. pull apart; ring constricts. complete.
cell. of FtsZ protein Membrane
forms. and cell wall
infold.
Controlling the cell cycle
Cell cycle Control System
Molecule cycling system for regulation
Checkpoints-points in the cycle where the cell is
halted until the go ahead chemical signal is
given (ex: G1 in animal cells is most critical)
Cell Cycle clock-Cyclin-dependent kinases
(Cdks) are protein kinases that need cyclin to
be active (regulating the levels of cyclin and
Cdks regulates the cell cycle)
Ex: MPF (maturation promoting factor)-cyclins
accumulate during the G2, making Cdks activate
which initiate Mitosis. This is turned off during the
M phase when proteolytic enzymes break down the
cyclin, allowing the cell to proceed through
anaphase
Figure 11-14
Cyclin concentration regulates MPF concentration.

G1 S G2 M phase G1 S G2 M phase G1 S

MPF component concentration

MPF activated by MPF activated by
dephosphorylation dephosphorylation
of MPF Cdk P of MPF Cdk P

MPF Cdk

in
ycl
C
PF
M

Time

Activated MPF has an array of effects.

Phosphorylate chromosomal
Activated MPF proteins; initiate M phase

P Phosphorylate nuclear
lamins; initiate nuclear
Cyclin Cdk envelope breakdown
Phosphorylate microtubule-
associated proteins. Activate
mitotic spindle?
Cyclin + Cdk with P Phosphorylate an enzyme
dephosphorylated,
that degrades cyclin; cyclin
cyclin-dependent
concentrations decline
kinase subunit
Internal and External Regulating
Cues
Internal Cues
Ex: M-phase checkpoint which occurs at
Metaphase and ensures that all chromosomes
are attached to spindles
Kinetochores that arent attached to spindles
send signals halting anaphase until theyre
attached
External Cues
Growth factors released from other body cells
Density-dependent inhibition-in Biology, we
called this contact inhibition (when cells are lost,
the Growth factor level increases so cells grow
and divide)
Figure 11-18

THE G1 CHECKPOINT IS SUBJECT TO SOCIAL CONTROL

Cy
cli
Cyclin n P
Cyclin Cdk
P
in G1 checkpoint
ycl P P
C passed
Rb
Cyclin Cdk
P S-phase

Rb
E2F

E2
E2F ATP
F E2F
Rb ADP
F
E2 F
E2

1. Growth factors 2. Growth factors 3. Cyclin binds to 4. Cdk is activated 5. Rb releases E2F. 6. E2F enters
arrive from other cause increase in Cdk; Cdk is by dephosphorylation. nucleus and
cells. cyclin and E2F phosphorylated. It catalyzes triggers production
concentration. Rb inactivates E2F phosphorylation of Rb. of S-phase proteins.
by binding to it.
Cancer
Cells that are cancerous dont respond to the cells
normal controls of the cell cycle
Some cancerous cells divide continuously and spread
easily, while others stop completely at one of the
various checkpoints
Cancers can transform adjacent cells to form tumors
Benign=cells remain unchanged within the tumor
Malignant=tumor becomes invasive and impairs the
organs function
If cells break away from the tumor and spread
through the blood stream, we say they metastasize
Cell cycle and Cancer Animations:
http://science.education.nih.gov/supplements/nih1/ca
ncer/activities/activity2_animations.htm
Figure 11-17
Benign tumor

Normal cells

Benign tumor cells

may continue to
divide, but are not
invasive (they do not
spread from tumor)

Malignant tumor

Malignant tumor cells

divide and spread to
adjacent tissues and to
distant tissues through
lymphatic vessels and
blood vessels

Lymph vessel

Blood vessel

New tumor that has

formed in distant
tissue by metastasis
The Molecular Biology of Cancer
Scientists think that that oncogenes-are the cancer-
causing genes as well as random mutation from DNA
damage
Proto-oncogenes are the normal genes that code for
proteins that regulate the cell cycle
Tumor supressor genes inhibit cell division
There are generally 3 ways that protooncogenes
become oncogenes
DNA movement w/in a genome
Point mutations
Amplification of a proto-oncogene
The development of Cancer
Cancer requires multiple mutations and at
least 1 oncogene
Cancers can begin as benign polyps, tumors,
etc, but the longer that these exist, the longer
there is for the necessary mutations to
accumulate
Viruses also play a role in the development of
some cancers
Retroviruses have oncogenes that can be donated
to the host cell
The viral DNA may also be inserted in such a way
that it disrupts a tumor-supressing gene.
What about Genetic
Predisposition?
It makes sense, that if oncogenes are partially
responsible for cancer, that certain cancers should run
in families
Examples of cancers with a strongly-heritable
component are colorectal cancer and breast cancer
In Breast cancer, mutations in the BRCA1 or BRCA2
genes appear to be responsible for many breast
cancers
These genes play a role in the cells DNA damage
repair proteins
It makes sense, then, that avoiding mutagens would
lower the risk of cancer, even if one has the
mutations in his/her genome
Meiosis
Forms the precursors of gametes
(Cell goes from 2nn (x-shaped, 2
cells)n (l-shaped, 4 cells)
Occurs in 2 divisions: Meiosis I
(homologs line up during prophase I
and crossing over occurs) and Meiosis
II (looks the most like mitosis)
Figure 12-4l

PRIOR TO MEIOSIS MEIOSIS I

Chromosomes replicate, Homologous chromosomes separate.
forming sister chromatids.
Tetrad (4 chromatids from
homologous chromosomes)
Nuclear Chromatin Non-sister
envelope chromatids Spindle apparatus

Chiasma

1. Interphase: 2. Early Prophase I: 3. Late Prophase I: 4. Metaphase I: 5. Anaphase I:

Chromosomes replicate Chromosomes condense,
in parent cell, in nuclear envelope breaks up,
uncondensed state. spindle apparatus forms.
Synapsis of homologous
chromosomes.
Crossing over of Tetrads migrate to Homologs separate 6. Telophase I and
non-sister chromatids metaphase plate. and begin moving to
(often multiple cross- opposite sides of cell.
Cytokinesis:
overs between the Chromosomes move to
same chromatids). opposite sides of cell,
then cell divides.
Figure 12-4r

MEIOSIS II
Sister chromatids separate.

7. Prophase II: 8. Metaphase II: 9. Anaphase II: 10. Telophase II and

Spindle apparatus Chromosomes line Sister chromatids Cytokinesis:
forms. up at middle of cell separate, begin Chromosomes move to
(metaphase plate). moving to opposite opposite sides of cell,
sides of cell. then cell divides.
Genetic Variation
Crossing over
Synapsis of homologs during prophase I causes
tetrads with chiasmata (crossing-over of
chromatids from neighboring chromosomes),
which mixes up sections of the chromosome
between homologs
Used to make linkage-maps
Independent assortment
Inheritance of one chromosome doesnt affect
the inheritance of another (non-linkage)
Random fertilization
You never know which resultant sperm will
fertilize which resultant egg
Figure 12-7-2

A CLOSER LOOK AT THREE KEY EVENTS IN MEIOSIS

Centromere
3. Crossing over, during prophase I.
Complex of proteins forms where
Non-sister crossing over will occur. Chromosome
chromatids segments are swapped between
non-sister chromatids.
Protein complex

Crossing over usually occurs at least

once in each non-sister chromatid,
but is only shown on 1 pair here