Mitosis: Chapter 10
Meiosis: Chapter 11
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Cell division
PSO:
Wednesday
11:30 Lilly 1-105
1:30 Lilly G-126
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- Melanoma, a type of skin cancer cause by uncontrolled growth of melanocytes
 Reproduction is a key element of life
 Requires 3 things:
1.
Replication of genetic material
2.
Accurate segregation of genetic material
3.
Division of cytoplasm
 Process needs to be controlled
 Responsive to environmental conditions
Bacteria divide by binary fission
 Prokaryotes have simple form of cell division
 DNA duplication and segregation a concerted process, are coupled
 Lot less genetic material than eukaryotes o Usually singular, circular chromosome
 Replication begins at unique site o Origin of replication o Bidirectional to unique site: terminus
Prokaryotic Chromosome compaction
 Chromosome larger than cell
 Chromosome must be compacted, folded o Complex with proteins o Supercoiled by topoisomerase
 Problem for replication and segregation
 Chromosome is also attached to plasma membrane
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Binary fission
 Segregation once thought to be passive o Now known to be an active process o Replicated DNA actively partitioned to different ends of cell o Requires specific sequences near origin
 Growth of new membrane and a septum partitions of other cell contents o Septum forms at site of ring of FtsZ protein o FtsZ resembles microtubule protein tubulin involved in eukaryotic mitosis
 Figures 10.1, 10.2
Eukaryotic chromosomes
 Homologue: same chromosome, different parent
 Sister chromatid: one of two exact copied of a replicated chromosome
 Centromere: visible constriction (near center of chromsome, not always in center) o Short repeated DNA sequences
 Kinetochore: proteins attached to centromere o Connect chromosomes to microtubules during mitosis
 Cohesin: complex of proteins holding sister chromatids together
 Figure 10.7
Problems cells must solve
 Chromosome compaction o Chromosomes are too long to fit into cell
 Means must always be folded o Even greater compaction for separation
 Replication and chromosome separation occur at different times o Chromosomes are not “labeled” o Means must keep chromatids of chromosomes attached until separation o Release of attachment is irreversible
 Cleavage of cohesin
2

Eukaryotic Chromosome compaction
 Chromosomes are very long and must be condensed to fit within the nucleus o DNA is complexed with histone proteins o DNA are – charged; histones are + charged
 Nucleosome – DNA wrapped around a core of 8 histone proteins
(histone octamer)
 Nucleosomes are spaced 200 nucleotides apart along the DNA
 Nucleosome compaction: Figure 10.5
The solenoid
 Further coiling of nucleosomes creates the 30-nm fiber (diameter) or solenid o Interphase compaction
 Further coiling of solenoid o Further compaction prepares for cell division o Forms radial (chromosomal) loops, are held in place by scaffold proteins o Scaffold proteins aided by condensin proteins o Radial loops staked on one anotherThe final prduct: Figure 10.4
Eukaryotic cell cycle
 The eukaryotic cell cycle has 5 main phases:
1.
G
1
(Gap phase 1)
2.
S (Synthesis)
3.
G
2
(Gap phase 2)
4.
M (Mitosis)
5.
C (Cytokinesis)
 Phases 1 – 3 = Interphase
 Cycle is oscillation: Mitosis and Interphase
 G
0
is nondividing, functional state at end of G
1
 The length of a complete cell cycle varies greatly among cell types
 5 Phases of the cell cycle: Figure 10.8
Interphase
 Interphase is composed of:
 G
1
(Ga phase 1) – time of cell growth
 S phase – synthesis of DNA (DNA replication)
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o 2 sister chromatids are produced o Centrosome (the two centrioles) replication
 G
2
(Gap phase 2) – chromosomes condense – become tightly coiled o Normal microtubule structure disassembled
 Differences in length of cell cycle mostly due to interphase (G
0
) length
Mitosis
 Mitosis is divided into 5 phases:
1.
Prophase
2.
Prometaphase
3.
Metaphase
4.
Anaphase
5.
Telophase
 Mitosis is a continuous process
Prophase
 Chromosomes continue to condense
 Centrioles move to each pole of the cell
 Spindle apparatus assembly o Microtubule bridge structure that forms between the two paired centrioles o Will later separate sister chromatids
 Nuclear envelope dissolves
 Figure 10.11
4

Prometaphase
 Additional microtubules grow and attach to sister chromatids at their kinetochores o Kinetochore microtubules
 Each sister chromatid captured by a microtubule from opposite sides of the cell
 Microtubules begin to pull each chromosome toward the center of the cell
 Figure 10.11
Metaphase
 Microtubules pull the chromosomes to align them at the center of the cell
 Once aligned, chromosomes under tension
 Check for accuracy
 Metaphase plate: imaginary plane through the center of the cell where the chromosomes align
 Figure 10.12
Anaphase
 Lysis of cohesion proteins causes the sister chromatids to separate
 Microtubules pull sister chromatids toward the poles
 In Anaphase A, the chromatids are pulled apart
 In Anaphase B, the poles move apart and the cell elongates
Telophase
 Spindle apparatus disassembles
 Nuclear envelope forms around each set of chromosomes
 Chromosomes begin to reverse the compaction process
(chromosomes no longer visible)
 Gene expression proceeds
 Nucleolus (where ribosomes are assembled) reappears in each new nucleus
 Opposite of Prophase
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Cytokinesis
 Cytokinesis – cleavage of the cell and cytoplasm into two equal cells
 In animal cells – Uses a contractile ring o Made of actin/myosin microfilaments (parts of the cytoskeleton) o Produces a cleavage furrow
 In plant cells – plasma membrane forms between the nuclei o Vesicles (made of a phosolipid bilayer) form, line up and fuse o Called a cell plate
 Figure 10.14, Figure 10.15
Phosphorylation
 Phosphorylation – addition of a phosphate group to a molecule o Kinases: enzymes that phorphorylate other molecules o (Phosphatases dephosphorylate other molecules)
 Phosphorylation is an important mechanism of regulating genes
 Cell cycle controlled by phosphorylation
Control of cell cycle
 Cell cycle controlled at three checkpoints:
1.
G
1
/S checkpoint: a.
The cell “decides” to divide
2.
G
2
/M checkpoint: a.
The cell makes a commitment to mitosis
3.
Late Metaphase (spindle) checkpoint: a.
The cell ensures that all chromosomes are attached to the spindle
 Figure 10.18
Cyclins
 Cyclins: regulatory proteins that are accumulated in a cell-cycle specific fashion o Increased going into mitosis o Degraded coming out of mitosis
 Cyclin-dependent kinases = Cdk’s o Kinase that only work when bound to cyclin o Cause an increased synthesis of cell cycle-specific proteins
6

Cyclins and Cdks
 Cdks function to trigger mitosis
 Cdks also controlled by phosphorylation o Activated by dephosphorylation o Active kinase -> drives mitosis
 Sensitive to internal and external factors o Nutritional state o Hormones and growth factors
 Figure 10.19
 Cell Cycle Control: Figure 10.21
G
1
/S checkpoint
 At G
1
/S Checkpoing: o G
1
cyclins (cyclin E) accumulate o G
1
cyclins bind with cdk2 to create the active G
1
/S Cdk o G
1
/S Cdk phosphorylates a number of molecules that ultimately increase the enzymes required for DNA replication
 G
2
/M checkpoint similar in nature o Different type of cyclin and Cdk o Different triggers
Spindle Checkpoint
 At the spindle checkpoint o The signal for anaphase to proceed is transmitted through anaphase-promoting complex (APC)
 APC activates separase o Separase hydrolyses the cohesion proteins holding sister chromatids together
 APC also necessary to destroy Cdks so cell can exit mitosis
Mitosis vs. Meiosis
 Mitosis results in two identical diploid cells
 Meiosis produces four cells that are not identical to each other
 Meiosis involves two successive cell divisions o No DNA replication in between
 Result: reduction of the chromosome number from diploid to haploid o Meiosis = gamete production
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Two Parts to Meiosis
 Meiosis includes two rounds of cell division – Meiosis I and Meiosis II o Meiosis I is the key
 During Meiosis I, homologous chromosomes (homologues) become closely associated with each other o This is synapsis
 Proteins between the homologues hold them in a synaptonemal complex
 Figure 11.4
Meiosis I
 Meiosis I is significantly different from mitosis
 Key is the behavior of chromosomes during meiosis I o Prophase I: chromosomes coil, pair up & form synaptonemal complex o Homologous pair aligns at Metaphase I o Homologous disjoin during Anaphase I
 Each daughter cell gets 1 homolog for each chromosome (each with
2 sister chromatids)
 Figure 11.6
Telophase
 Telophase I: o Nuclear envelope form around each set of chromosomes o Each new nucleus s now haploid o Sister chromatids are no longer identical because of crossing over
 Cytokinesis follows telophase I
 Bried interphase with no S phase
8

Crossing Over
 Paired Homologous can exchange genetic material during meiosis I o Prophase I synaptonemal complex formed o Crossing over occurs o Physical exchange of chromosomal material o Chiasmata: site of crossing over
 Meiosis increases variation o Independent behavior of chromosomes o Crossing over rearranges chromosomes
 Figure 11.5
Crossing Over & Genetic Variation
 Generates additional genetic variation than from sexual reproduction alone (each offspring inherits only half of their genes from each parent)
 May result in new combinations of alleles on a particular chromatid
(those that had previously existed on non-sister chromatids)
 Only detected genetically if new combinations of alleles are generated on a chromosome
Meiosis II
 Meiosis I is followed by Meiosis II o No replication between
 Meiosis II is like a mitotic division without replication
 Each cell has only 1 homolog for each chromosome
 Sister chromatids separate during Anaphase II
Meiosis review
 Meiosis is characterized by 4 features:
1.
Synapsis and crossing over
2.
Sister chromatids remain joined at their centromeres throughout meiosis I
3.
Kinetochores of sister chromatids attach to the same pole in meiosis I
4.
DNA replication is suppressed between meiosis I and meiosis II
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