2. Cell Division; Mitosis
• Mitosis produces two identical daughter cells that
are exact replicas of the parental cell
• Most body cells are somatic cells (nonreproductive), usually with chromosomes present in
pairs, the number of chromosomes is the diploid
number (2n)
3. Cell Division (Reproductive Cells); Meiosis
• Meiosis produces gametes that have half the number of
chromosomes as the original cell: haploid (n)
• The gametes are not identical to one another
• Basis for sexual reproduction; genetic diversity is the
adaptive advantage of sex! Aids evolution!
4. Homologous Pair
• Diploid cells carry two sets of genetic information.
• Where are they coming from?
• Haploid cells carry one set of genetic information.
6. Homologous vs. Non-homologous
Chromosomes
Non-homologous Chromosomes
Homologous Chromosomes / Homologs
Homologous chromosomes (homologs) = members of a
chromosome pair that are identical in the arrangement of genes they
contain (but might have different alleles) – i.e. 2 copies of
chromosome #1. Homologs pair during meiosis!
Non-homologous chromosomes = chromosomes that contain
different genes and do not pair during meiosis
7. Gene Order on Homologous Chromosomes
Homologous chromosomes contain the same genes in the
same order
Gene A
Gene D
Gene B
Gene E
Gene C
Gene F
Are the DNA sequences of homologous completely identical?
No! can have different alleles!
8. Chromosome Structure Overview
• Centromere: attachment point for spindle microtubules
• Telomeres: tips of a linear chromosome. Provide
chromosomal stability
• Limits Cell Division; over time telomeres become shorter
• Aging and Cancer
• 2009 Nobel Prize awarded to E. Blackburn
• Origins of replication: where the DNA synthesis begins
11. What is a possible difference
between two homologs?
17% 17% 17% 17% 17% 17%
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A. Different genes
B. Different lengths
C. Different loci for
alleles
D. Different
centromere
positions
E. Different alleles
F. All of the above
12. 3.1 Mitosis Divides Somatic Cells
• Mitosis is the process of cell division
that produces two genetically identical
daughter cells from one original
parental cell
• It is precisely controlled to prevent
either an excess or insufficient number
of cells
• Rate of division is important
• Too slow: failure to develop, morphological
abnormalities
• Too fast: growth of structures beyond
boundaries (cancer!)
• Both: Death!
13. Stages of the Cell Cycle
• Cell division is regulated by
control of the cell cycle, a
cycle of DNA replication and
division
• Cell cycles of all eukaryotes
are similar
• The two principal phases of
the cell cycle are M phase,
the short time during which
the cells divide and a longer
interphase, the time between
M phases
15. Interphase
• During the Gap 1 (G1) phase of
interphase, all proteins needed
for normal cell function are
transcribed and translated; the
duration of G1 varies
• DNA is replicated during S
phase or synthesis phase,
which follows G1
•
Two sister chromatids are produced!
• A small number of cells enter G0
after G1; cells in G0 never
progress through the cell cycle
• The completion of S phase
leads into G2 or Gap 2 phase,
during which the cells prepare
for division
www.nature.com
16. DNA Replication
The chromosomes are replicated prior to cell division
1 chromosome
Circle 1 chromosome
after replication
Why?
Homologous
Chromosomes
What do you call these two identical strands?
The two strands are completely identical
17. Sister Chromatids
Non-sister chromatids
Sister Chromatids
Sister Chromatids: The 2 subunits of a replicated chromosome.
- They should be identical.
Non-sister Chromatids: chromatids from different chromosomes
Find a pair of non-sister chromatids
18. Sister Chromatids are IDENTICAL!
A
B
c
Homologous
before replication
Homologous
after replication
A
B
c
A
B
c
a
b
C
a
a
b
C
What alleles will be on
each chromatid?
b
C
If 1 sister has “A”, the other sister will too, etc
19. Chromosomes During Mitosis
• Cells at the beginning and the
end of mitosis are diploid (2n)
• Progressive condensation of
chromosomes begins in
prophase and reaches a
maximum in metaphase
• Centromeres, specialized
sequences where sister
chromatids are joined together,
become visible in prophase;
centromeres bind protein
complexes called kinetochores
DNA in blue
Microtubules in green
Kinetochores in pink
20. Substages of M Phase
• M phase is divided into
• Prophase
• Prometaphase
• Metaphase
• Anaphase
• Telophase
• M phase accomplishes karyokinesis, partitioning
of DNA into daughter cell nuclei and cytokinesis,
the partitioning of the cytoplasm
24. Chromosome Distribution
• In animal cells, two
centrosomes appear, which
migrate to form the opposite
poles of the dividing cell
• Centrosomes are the source
of microtubules;
microtubules have a minus (-)
end at the centrosome and a
plus (+) end that grows away
from the centrosome
• The spindle fibers emanate
from the centrosomes in a
pattern called the aster
25.
26. Types of Microtubules in Cells
1.
Kinetochore microtubules
embed in the
kinetochore at the centromere
of each chromatid,
and are responsible for
chromosome movement
2.
Polar microtubules extend
toward the opposite
pole of the centrosome and
contribute to cell
elongation and cell stability
3.
Astral microtubules grow
toward the membrane
of the cell, and contribute to
cell stability
27. Metaphase Chromosomes
• By the end of prometaphase,
kinetochore microtubules are
bound to each kinetochore
• Metaphase chromosomes
are 10,000-fold condensed
compared to the onset of
prophase; these
chromosomes are pulled
toward each centrosome by
the kinetochore microtubules
• The opposing forces align the
chromosomes along the
metaphase plate
http://staff.jccc.net/pdecell/celldivision/mitosis1.html
28. Sister Chromatid Cohesion
• Sister chromatid
cohesion
• Balances tension created
by pull of kinetochore
microtubules
• Cohesin holds sister
chromatids together,
preventing their premature
separation
• 4-subunit protein
• coats sister chromatids
along their entire length
• greatest concentration at
the centromeres
29. Anaphase
• Sister chromatids separate at
anaphase and begin to move
toward opposite poles in the
cell
• In anaphase A the sister
chromatids separate due to the
enzyme separase cleaving
Scc1, the central component of
cohesin
• The separation of sister
chromatids is called
chromosome disjunction
30. Anaphase, continued
• During anaphase, polar
microtubules extend in
length, causing an
extended shape
• The altered shape
facilitates cytokinesis at
the end of telophase,
leading to formation of
two daughter cells
31. Completion of Cell Division; Telophase
• In telophase, nuclear
membranes reassemble
around the chromosomes
at each pole
• Decondensation returns
chromosomes to their
diffuse interphase state
• Two identical nuclei
occupy the elongated cell
What’s Next?
32. Cytokinesis
• In animal cells, a
contractile ring of actin
creates a cleavage furrow
around the circumference
of the cell; this pinches
the cell in two
• In plants, a new cell wall
is constructed along the
cellular midline
• In both, cytokinesis
divided the cytoplasm and
organelles between the
daughter cells
33. Mitosis Produces
Identical
Daughter Cells
• Mitosis separates
replicated copies of
sister chromatids
into identical nuclei,
forming two
genetically identical
daughter cells
• The diploid number
of chromosomes
(2n) is maintained
throughout the cell
cycle
36. Cell Cycle Checkpoints
• Common, genetically
controlled signals drive the
cell cycle
• Cell cycle checkpoints are
monitored by protein
interactions for readiness to
progress to the next stage
• A common mechanism is
carried out by protein
complexes joining a protein
kinase with a cyclin protein
What happens if we
What happens if we
lose control of the
lose control of the
cell cycle?
cell cycle?
37.
38. Cyclins and Cdks
• Protein kinase
components of the
complexes are activated
by association with
cyclins and so are called
cyclin-dependent
kinases (Cdks)
• Multiple cyclin and Cdks
form a variety of
complexes
• For example, cyclin BCdk1 is required to
initiate M phase; the
complex also activates an
enzyme that degrades
cyclin B
39. Cyclins control the cell cycle.
WHAT IF WE LOSE CONTROL
OF THE CELL CYCLE?
HOW CAN WE ALTER THE
SPEED OF THE CELL CYCLE?
40.
41. The RB1 Gene Is a Tumor Suppressor Gene
• The unphosphorylated Retinoblastoma protein
(pRB) acts like a brake on the cell cycle, preventing
progression to S phase
• It is one of many proteins known as tumor
suppressors, with roles in blocking the cell cycle
• The gene RB1, which produces pRB, is a tumor
suppressor gene
42.
43. Proto-oncogenes are the green light for the cell cycle!
Proto-oncogenes are the green light for the cell cycle!
44. The Cyclin D1 Gene Is a Proto-Oncogene
• The gene cyclin D1
leads to formation of
the cyclin D1-Cdk4
complex that
stimulates the cell
cycle to enter S phase
• Cyclin D1 is a protooncogene, defined as
a gene that when
expressed stimulates
cell cycle progression
45. Cell Cycle Mutations and Cancer
• Normal cells proliferate only when needed, in response to
signals from growth factors
• They are also responsive to neighboring cells; growth is
moderated to serve the best interests of the whole organism
• Cancer is characterized by out-of-control
proliferation of cells that can invade and
displace normal cells
46. Oncogenes are the gas pedal STUCK ON!
Oncogenes are the gas pedal STUCK ON!
47. Mutations Related to Cancer Development
• Cancer-causing mutations alter cyclin D1Cdk4 and pRB interactions
• Some mutations increase the number of
copies of cyclin D1, now an oncogene!
• Higher-than-normal levels of cyclin D1
promote uncontrolled entry into S phase,
due to constant phosphorylation of pRB
http://www.broadinstitute.org
48. Mutations Related to Cancer Development
• Another mutation affects
RB1; it produces a pRB
that binds weakly or not at
all to E2F
• Can lead to uncontrolled
entry into S phase
• This is loss of a tumorsuppressor gene!
• Several types of cancers
are associated with RB1
mutations, including
retinoblastoma, and
bladder, lung, bone, and
breast cancers
51. 3.2 Meiosis Produces Gametes for Sexual
Reproduction
• Reproduction can be divided into
two broad categories:
• In asexual reproduction,
organisms reproduce without
mating and produce genetically
identical offspring
• In sexual reproduction, gametes
(reproductive cells) are produced;
these unite during fertilization
52. Multicellular Eukaryotes Reproduce Mainly
Sexually
• Males and females
carry distinct
reproductive tissues
and structures
• Mating requires the
production of haploid
gametes from both
male and female
• The union of haploid
gametes produces
diploid progeny
53. Meiosis versus Mitosis
• Meiosis is distinguished
from mitosis as it results
in the production of four
haploid gametes
• Meiotic interphase is
followed by two division
stages called meiosis I
and meiosis II.
• No DNA replication
between these stages!
54.
55. Meiosis I vs. II
In meiosis I Ihomologous
In meiosis homologous
chromosomes separate;
chromosomes separate;
reducing the diploid number
reducing the diploid number
of chromosomes to the
of chromosomes to the
haploid number
haploid number
In meiosis II,
In meiosis II,
sister
sister
chromatids
chromatids
separate to
separate to
produce four
produce four
haploid
haploid
gametes
gametes
56. Meiosis I
• Three hallmark events
occur in meiosis I
1. Homologous
chromosome pairing
2. Crossing over between
homologous
chromosomes
3. Segregation
(separation) of
homologous
chromosomes, which
reduces chromosomes
to the haploid number
57. Stages of Meiosis I
• Meiosis I is divided into prophase I, metaphase I,
anaphase I, and telophase I
• Pairing and recombination of homologs takes
place in prophase I
• Prophase I is subdivided into five stages:
leptotene, zygotene, pachytene, diplotene, and
diakinesis
60. Synaptonemal complex:
-occurs between nonsister chromatids of homologous chromosome
-contains the recombination nodule, essential for crossing over of genetic
material
61.
62. Metaphase I
• In metaphase I
chiasmata between
homologs are dissolved;
this completes crossing
over
• Homologs align on
opposite sides of the
metaphase plate
http://www.phschool.com
63. Anaphase I
• Anaphase I begins when homologs separate from
one another and are pulled to opposite poles of
the cell
• Sister chromatids are firmly attached by cohesin
http://www.phschool.com
64. Telophase I and Cytokinesis
• In telophase I the nuclear membranes reform around
the separated haploid sets of chromosomes
• Cytokinesis follows telophase I and divides the
cytoplasm to create two haploid cells
• Meiosis I is called the reductional division because
the ploidy of the daughter cells is halved compared
to the original diploid parent cell
66. Meiosis II
• Meiosis II divides each haploid daughter cell into two haploid cells, by
separating sister chromatids from one another
• The process is similar to mitosis in a haploid cell
• Four genetically distinct haploid cells are produced, each carrying one
chromosome of a homologous pair
67.
68. The Mechanistic Basis of Mendelian Ratios
• Separation of homologs and sister
chromatid in meiosis constitutes the
mechanical basis of Mendel’s laws
• For example, in an organism that is genotype Aa, the
homologs bearing A and a separate from one another
during anaphase I
• At the end of meiosis, two gametes have the A allele
and two have a; this generates the 1:1 ratio predicted
by the law of segregation
2.6 Diploid eukaryotic cells have two sets of chromosomes. (a) A set of chromosomes from a female human cell. Each pair of chromosomes is hybridized to a uniquely colored probe, giving it a distinct color. (b) The chromosomes are present in homologous pairs, which consist of chromosomes that are alike in size and structure and carry information for the same characteristics. [Part a: Courtesy of Dr. Thomas Ried and Dr. Evelin Schrock.]
2.7 Each eukaryotic chromosome has a centromere and telomeres.
2.8 Eukaryotic chromosomes exist in four major types based on the position of the centromere. [Micrograph by L. Lisco, D.W. Fawcett/Visuals Unlimited.]
Table 2.1 Features of the cell cycle
2.12 The number of chromosomes and the number of DNA molecules change in the course of the cell cycle. The number of chromosomes per cell equals the number of functional centromeres, and the number of DNA molecules per cell equals the number of chromatids.