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Transcript
Cellular Reproduction
(Mitosis)
Anderson
Spring 2017
College of the Redwoods
Cell Division
• Why do cells need to divide?
• Single-celled organisms – cell division is their method of
reproduction
• Make an exact copy of themselves
• Little genetic variation (unless mutations occur)
• Multicellular organisms – necessary for repair, tissue
regeneration, and growth
• Ex: Blood and skin cells constantly being produced
• Zygote (single cell from egg/sperm fusion) must divide trillions
of times to create multicellular organism
Genomic DNA
• Genome – a cell’s complete complement of DNA
• Prokaryotes – one circular double-stranded DNA molecule
• Eukaryotes – several linear double-stranded DNA molecules
bound with proteins (chromosomes)
• Each species has a characteristic number of chromosomes
• Each cell has 2 matched sets of chromosomes
Species
# of total
chromosomes
# of sets of
chromosomes
Human
46
23
Cat
38
19
Dog
78
39
Fruit Fly
8
4
Diploid vs Haploid
• We use the letter n to represent a single set of chromosomes
• Diploid – 2 matched sets of chromosomes, 2n
• Humans have 46 total chromosomes in somatic cells (non-sex
cells)
• Haploid – one set of
chromosomes, n
• Humans have one set
of 23 chromosomes in
gametes, or sex cells
(egg and sperm)
Homologous Chromosomes
• Matched pairs of chromosomes
in diploid organism
DNA wound
up tightly
Locus 1
• Same length (except X/Y)
• Have specific nucleotide
segments (gene) in the same
location (locus)
Genes
Locus 2
• Each copy originates from a
different parent
From Mom
From Dad
Homologous Pair
Cell Cycle
• Ordered series of events involving cell growth and cell
division (eukaryotes)
2 Phases:
1. Interphase – cell
grows and DNA is
replicated
2. Mitotic phase –
replicated DNA and
cytoplasmic contents
are separated and
cell divides
Interphase
• Cell undergoing normal processes while preparing for cell
division
• When cell is not preparing to divide it’s just undergoing normal
processes (“resting” state)
• G1 Phase (1st gap)
• Cell accumulating building blocks of
chromosomal DNA and associated
proteins
• Obtaining enough energy reserves to
replicate each chromosome
Interphase
• S Phase (synthesis
phase)
• DNA replication
• Makes identical
copies of each
chromosome
(sister
chromatids)
• Firmly attached at
centromere
• Semi-condensed chromatin
configuration (can’t see it under
microscope yet)
S Phase Cont’d
• Centrosome also duplicated
• Microtubule bundle that’s
part of the cytoskeleton
• Centrosomes has pair of centrioles
that help organize cell division
• The 2 centrosomes make up the
mitotic spindle
Interphase
• G2 Phase (2nd gap)
• Cell replenishes its energy
stores
• Synthesizes proteins necessary
from chromosome
manipulation
• Some organelles are duplicated
• Cytoskeleton dismantled to
provide resources to mitotic
spindle
Mitotic Phase
• To make 2 daughter cells (make exact copy)
• Contents in cell’s nucleus and cytoplasm must be divided
• Duplicated chromosomes line up, separate and move to
opposite poles
1. Mitosis – 5 state process which accomplishes nuclear
division
2. Cytokinesis – physical separation of cytoplasmic
components into 2 cells
Mitosis
5 Stages of Mitosis
1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase
Prophase
• Nuclear envelope (membrane) starts to break into small vesicles
• Golgi apparatus and endoplasmic reticulum fragment and disperse
to periphery
• Centrosomes begin to move to opposite poles, microtubules extend
• Nucleolus disappears
• Sister chromatids coil
more tightly (visible under
microscope)
Prometaphase
• Remnants of nuclear envelope disappears
• Microtubules stretch across former nuclear
area
• Chromosomes become more condensed
• Each sister chromatid
attaches to spindle
microtubules at
centromere via
kinetochore (protein
complex)
Metaphase
• Chromosomes align in a plane (metaphase plate)
• Midway between the 2 poles
• 2 kinetochores of each chromosome attached to microtubule
at opposite poles
• Spindle checkpoint –
ensures chromatids
will split evenly
Anaphase
• Sister chromatids split apart at centromere (now
chromosomes again)
• Chromosomes pulled toward respective centrosome
• Microtubules not attached to chromosome push poles apart
to make cell longer
Telophase
• When chromosomes reach opposite pole they decondense
• Mitotic spindles broken down – will be used to build new
cytoskeleton
• Nuclear envelope
forms around
chromosomes (both
copies)
Cytokinesis
• Physical separation of cytoplasmic components of 2
daughter cells
• Very different for cells with cell wall vs. no cell wall
Cytokinesis without Cell Wall
• Begins after the onset of anaphase
• Contractile ring (actin filaments) form inside along former
metaphase plate
• Actin filaments pull equator of
cell inward forming cleavage
furrow
• Think of belt around “waist” of
cell being pulled tighter until the
cells split
Cytokinesis with Cell Wall
• Rigid cell wall prevents the “belt tightening”
• New cell wall must form between the cells
• The Golgi vesicles (vesicles contained broken down Golgi
apparatus) collect on metaphase plate
• Vesicles fuse to form cell plate
• Cell plate will grow until it
merges with outer cell wall
• Accumulated glucose build new
cell wall of cellulose
G0 Phase
• Most of the time, newly formed daughter cells immediately
enter interphase followed by mitotic phase
• But some cells go into a state of “rest” – not actively
preparing to divide
• Cells that never or rarely
divide remain in G0
permanently
Internal Checkpoints
• Mistakes in duplication or distribution of chromosomes can
lead to mutations that can be passed on to new cells
• Checkpoints are internal control
mechanisms that can stop the
cell cycle during unfavorable
conditions
• These happen:
• Near end of G1
• End of G2
• During metaphase
Internal Checkpoints
• G1 Checkpoint – determines whether all conditions are favorable
for cell division
• Point where cell irreversibly commits to cell division
• Check for genomic DNA damage
• Checks for adequate reserves and cell size
• G2 Checkpoint – stops entry into mitotic phase
• Cell size and protein reserve is assessed
• Most importantly, ensures that all chromosomes have been replicated
and DNA is not damaged
• M Checkpoint – end of metaphase (spindle checkpoint)
• Determines if sister chromatids are correctly attached to spindle
microtubules (separation during anaphase is irreversible)
What happens when the
checkpoints fail?
• Even with the checkpoint in the S phase (when DNA gets copied) a
small % of replication errors still occur
• If the error occurs in a nucleotide sequence
of a gene, a gene mutation results
• Over and over, small uncorrected errors are
passed from parent to daughter cell and
accumulate with each generation
• If the mutation renders protein nonfunctional, the cell will die
• Sometimes a mutation increases cell cycle
activity
Cancer
• Cancer starts when the mutation gives rise to a faulty protein
involved in cell reproduction
• Uncontrolled growth of mutated cells outpaces growth of
normal cells (cell cycle sped up)
• Proto-oncogenes – genes that code for positive cell-cycle
regulators
• Oncogenes – mutated proto-oncogenes that cause cell to
become cancerous
• Cells can be pushed past their checkpoints to rapidly divide
Cyclin-dependent kinase (Cdk)
• Cyclins are cell cycle regulators
• They bind to Cdk to activate enzymes involved in DNA replication
• When a mutation causes Cdk to be activated before it should be, it
can push the cell cycle past a checkpoint
• Cdk is a protooncogene
• Once Cdk is altered
to increase rate of
cell cycle it becomes
an oncogene
P53
• Tumor suppressor gene – gene that codes for negative
regulator proteins, like P53
• When the genes are activated, uncontrolled cell division can
be controlled
• Mutated P53 genes have been identified in more than half of
all human tumor cells
• Damaged P53 allows
mutations to continue
Prokaryotic Cell Division
• Cell division is only method of reproduction for unicellular
organisms
• Daughter cell becomes new organisms
• Since there’s no nucleus or multiple chromosomes, mitosis is
unnecessary
• Prokaryotes use binary fission for cell division
• Like mitosis, all DNA is copied and cytoplasmic contents
divided
Binary Fission
• DNA replication starts at origin and
replicates in both directions
• Each origin point moves towards cell
ends, elongating cell
• Septum forms between nucleoids (cell
wall)
• When new cell walls are in place, the
cells separate