OVERVIEW
• DNA replication
• Overview of cell division
• Mitosis
• Meiosis
DNA
REPLICATION
Occurs during interphase of cell
cycle
1 DNA molecule untwisted
Each parent strand serves as
template for new strand
= 2 new DNA molecules,
each ½ old & ½ new
= semi-conservative replication
Enzymes break H bonds between 2
strands
= unwinds & exposes nucleotide bases
Free nucleotides pair with exposed
bases
Each parent strand has new one
made on it
= twist together to form double helix
DNA REPLICATION IN A
LITTLE MORE DETAIL …
Sugar-phosphate backbones of 2 DNA strands run
in opposite directions
5’ end
= Phosphate group on sugar’s C
3’ end
= –OH group on sugar’s C
DNA polymerase adds nucleotides to 3’
ends only
Daughter strand grows in 5’ to 3’ direction
REPLICATION ENZYMES:
HELICASES
Catalyze breaking of H bonds so double helix can
unwind
Work with small proteins to prevent rewinding of
parent strands
REPLICATION ENZYMES:
DNA POLYMERASES
Catalyze addition of free nucleotides to exposed bases
on each strand
Also have proofreading abilities
REPLICATION ENZYMES:
DNA LIGASES
Work on discontinuously-assembled
strand
Seal together short stretches of new
nucleotides
TRANSCRIPTION VS. DNA
REPLICATION
Transcription
DNA replication
Only part of DNA
strand unwound
Whole DNA
molecule unwound
RNA polymerase
adds nucleotides
to growing strand
DNA polymerase
adds nucleotides to
growing strand
Results in 1 free
mRNA strand
Results in 2 doublehelix DNA
molecules
Mistakes occur that can be lethal if not caught
e.g. wrong base-pairing
DNA proofreading mechanisms fix most
replication errors & breaks in strands
(proofread & correct mismatches)
Repair enzymes repair some changes by
snipping out damaged sites or mismatches
If mismatch can’t be fixed, replication is stopped
CELL DIVISION: AN
OVERVIEW
Parents reproduce to produce new generation of cells
or multicellular organism
Offspring inherits all information & metabolic
machinery from parent
EUKARYOTIC CELL
DIVISION
DNA in eukaryotic cells is in nucleus
Eukaryotic cells can’t divide by fission
Must copy & package DNA into > 1 nucleus before
cytoplasm can split
TWO TYPES OF CELL DIVISION
Mitosis:
• Produces 2 genetically identical cells
• Happens throughout body
Meiosis:
• Produces 4 genetically different cells
• Cells only have ½ of genetic info
• Happens only in gonads
MITOSIS
One part of the cell cycle
Growth, cell replacement, tissue repair
Also used for asexual reproduction
= organisms clone selves
Unique to eukaryotes
THE CELL CYCLE
The period from one cell division to next
INTERPHASE: THE LONGEST
PHASE
90% of cell cycle length
Interphase
G1: GAP / GROWTH
PHASE
Cell growth
# of cytoplasmic components
doubled
S: SYNTHESIS PHASE
DNA duplicated
Chromosome & copy = sister chromatids
Joined at centromere
G2: GAP OR GROWTH
PHASE II
Makes proteins necessary for
cell division
Cell prepares to divide
Cells stay in G1 if making macromolecules
Enter S when DNA & accessory proteins are copied
Rate of DNA replication is same for all cells of a species
Same cycle length for same type of cells
Different cycle lengths for different types of cells
e.g. cells in red bone marrow divide every second
e.g. nerve cells stay in G1 indefinitely
Rate of cell division is under control
(checkpoints, molecular brakes, etc.)
After G2, cell enters mitosis
Mitosis maintains cell’s chromosome #
CHROMOSOME NUMBER
Humans have 46
chromosomes
= diploid (2n)
2 of each type of
chromosome
= one set from mother,
one from father
During mitosis:
Each 2n parent cell produces two 2n daughter cells
Each daughter cell has each pair of chromosomes
= 23 pairs
During mitosis, 2 sister chromatids (duplicated
chromosomes) separate
Each becomes independent chromosome that ends up in 1
of daughter cells
THE
MITOTIC
SPINDLE
Present in every cell
Made of microtubules
= change length by addition or
removal of tubulin subunits
Originates from pair of centrioles
Early in cell division, duplicated
chromosome is condensed =
coils up
DNA winds twice around histones
= nucleosome
Keeps chromosomes organized
during nuclear division
LATE INTERPHASE /
PRE-PROPHASE
Outside of nucleus, 2 centrioles duplicate
selves
EARLY PROPHASE
Inside nucleus:
Chromosomes begin to condense
Outside nucleus:
Spindle begins to form
Nuclear envelope begins to fall apart
LATE PROPHASE
Nuclear envelope completely falls apart
Spindle fibres from each pole attach to
sister chromatids of each chromosome
METAPHASE
Chromosomes line up halfway between
spindle poles
ANAPHASE
Sister chromatids of each chromosome
separate & move to opposite poles
(motor proteins attached to kinetochores
drag chromatids along microtubules)
Spindle poles pushed apart by growing
microtubules
TELOPHASE
1 of each type of
chromosome reaches each
spindle pole
= 2 identical groups of
chromosomes at each cell pole
Chromosomes decondense
Nuclear envelope forms around
each cluster of chromosomes
= two nuclei, each with 2n # of
chromosomes
CYTOKINESIS
Cytoplasm of cell divides
Results in 2 daughter cells, each with same
number of chromosomes as parent cell
CYTOKINESIS IN ANIMAL
CELLS
Contractile ring mechanism
Halfway between cell’s
poles, plasma membrane
constricts = cleavage
furrow
(ATP energy causes
contraction of actin
filaments)
CYTOKINESIS IN PLANT
Cell plate formation
CELLS
Golgi vesicles move to
cell equator & fuse
Vesicle membranes
become cell membranes
Contents become
cellulose cell wall
SUMMARY OF MITOSIS
Nuclear & cellular division that
maintains chromosome #
Used for growth, repair, asexual
reproduction
Cell division & DNA replication regulated so that:
DNA only replicated once before cell division
Cells that never divide do not replicate DNA
Cells don’t try to replicate DNA if lack the energy & raw
materials to complete process
CELLULAR CONTROLS
OVER MITOSIS
Anchorage dependence
Animal cells must be in contact with a
solid surface to divide
Density-dependent inhibition
Crowded cells stop dividing
Growth factors
Required to start & continue dividing
Secreted by other cells
CELL CYCLE
CHECKPOINTS
Cell cycle has checkpoints:
– Structure of chromosomal DNA monitored
– Completion of phases monitored
– Determines if good time for cell division
Rely on internal & external cues
G1 checkpoint is most important:
If no go-ahead signal, cell will switch to nondividing G0 phase
e.g. nerve & muscle cells remain in G0 indefinitely
CANCER & CELL DIVISION
If immune system doesn’t recognize &
destroy a cancerous cell, it may divide
multiple times & form a tumor
Benign
Cells remain localized
Malignant
Spreads to other parts of body & disrupts
function
WHY DON’T CANCER CELLS FOLLOW
THE RULES?
Don’t exhibit density-dependence
Have defective control systems
Ignore / over-ride checkpoints
Some synthesize own growth factors so continue dividing
Divide indefinitely
TYPES
OF CANCERS
Carcinomas
Internal & external coverings of body e.g. skin
Sarcomas
Supportive tissues e.g. bone & muscle
Leukemias & Lymphomas
Blood-forming tissues e.g. bone marrow, spleen, lymph
nodes
WAYS TO TREAT
CANCER
If not severe:
Surgical removal of tumor
Radiation therapy
(damages DNA of cancer cells to greater degree than
normal cells)
If severe:
Chemotherapy
Uses drugs to disrupt cell division
e.g. Paclitaxel freezes the mitotic spindle at
metaphase
e.g. Vinblastin prevents spindle formation
Also affects rapidly-dividing normal cells e.g.
intestinal lining, immune cells, hair follicle cells
CLONING
Donor cells from 1
animal starved
so enter nondividing G0 phase
Nucleus removed
from unfertilized
egg cell of
another animal
Donor cell & egg cell placed next to each
other in culture dish & electrically
stimulated
Cells fuse & enter mitosis
Cell continues mitotic divisions & forms
embryo
Embryo implanted into surrogate mother
(same spp. as egg cell)
Surrogate mother gives birth to genetic twin
Mitosis:
• Occurs in somatic
MITOSIS
VS.
cellsMEIOSIS
• Results in 2 genetically identical cells
• Growth, cell replacement, tissue repair
= asexual reproduction
Meiosis:
• Occurs in sex cells
• Results in 4 genetically different cells with ½ genetic info of
parent cell
= sexual reproduction
ASEXUAL VS. SEXUAL
REPRODUCTION
Asexual reproduction:
Individual makes multiple offspring with
identical DNA
Sexual reproduction:
Allows for variety in heritable traits
Adaptive in changing environments
Meiosis → formation of gametes →
fertilization
THE EUKARYOTIC
CHROMOSOME
Double-stranded DNA & associated
proteins
Chromosomes duplicated during
Unduplicated
interphaseDuplicated
Centromere
Sister chromatids
CHROMOSOME NUMBER
Almost every cell in body has 2 complete sets of
chromosomes
One set from mother, one from father
2 sets = diploid (2n)
Each cell has 2 versions of each gene
Homologous chromosomes
Pair of chromosomes that carry genes for same heritable
traits
Except sex chromosomes (X or Y)
GENES
Sequences of chromosomal DNA
Contain heritable information to
make new individuals
Individuals have pairs of genes on
pairs of chromosomes
Each member of pair of gene = allele
One of the variant forms of a gene
at a
ALLELE
particular (locus) location on a chromosome
Different alleles produce variation in inherited
characteristics (e.g. hair & eye colour, etc.)
Basis for evolution: endless combinations of
alleles lead to variations in traits
SO WHAT IS MEIOSIS?
Nuclear division that halves
chromosome #
Occurs only in sex (reproductive) cells
1st step in formation of gametes (
)
Gametes fuse with opposite sex
or
Humans are diploid (2n) with 46 chromosomes
(23 + 23 homologous chromosomes)
Meiosis halves chromosome number so daughter cells
(gametes) are haploid (n) with 23 chromosomes
GAMETES
Have only 1 set of chromosomes
= haploid (n)
Each gamete has 1 allele for each gene
In humans = eggs or sperm
During meiosis, one cell goes through 2 divisions to
end with formation of 4 cells, all with haploid (n)
nuclei
INTERPHASE
Same as in mitosis:
Cell grows & duplicates cytoplasmic
components
DNA is replicated
PROPHASE I
Chromosomes condense
Crossing-over occurs between
homologous chromosomes
Centrioles move to opposite sides of
nuclear envelope
Nuclear envelope begins to fall apart
CROSSING OVER
When chromosomes condense during prophase,
homologous chromosomes stick very closely together
& form a tetrad
Maternal & paternal chromosomes swap
genes
= exchange segments of genetic info
Homologous chromosomes become mixture
of maternal & paternal info
chiasma
METAPHASE I
Homologues of chromosomes tethered
by microtubules at opposite spindle poles
Chromosomes line up along equator of
cell
ANAPHASE I
Chromosomes pulled apart & move towards
respective poles
Poles move further apart
TELOPHASE I
Cytoplasm divides
Results in 2 haploid cells
(only have 1 of each pair of homologous
chromosomes)
Chromosomes still duplicated
PROPHASE II
New mitotic spindle forms in each
cell
Chromatids of each chromosome
become tethered to opposite poles
METAPHASE II
Chromosomes line up along equator of cell
ANAPHASE II
Chromatids separate & move towards opposite
poles
Spindle poles pushed apart
TELOPHASE II
Nuclear envelope forms around each chromosome
cluster
CYTOKINESIS
Cytoplasm divides
Results in 4 haploid (n) daughter cells
Chromosomes are unduplicated
MEIOSIS—THINGS TO PAY ATTENTION
TO:
1. DNA replication:
a. Occurs only during interphase before Meiosis I
2. Meiosis I
a. Prophase: crossing-over
b. Metaphase: line up in 2 rows
c. Anaphase: separation of homologous
chromosomes
3. Meiosis II
a. Similar to mitosis but no interphase precedes it
b. Division results in haploid cells
MEIOSIS & TRAIT
VARIATION
Can occur via:
• Crossing over
• Random alignment of
chromosomes at metaphase I
A. CROSSING
OVER
Exchanges of allele-containing
segments
occurs
between non-sister chromatids (i.e. between
maternal & paternal chromosomes)
Gene-swapping: different versions of heritable
information are swapped
= leads to recombination of genes & variation in
traits
B. METAPHASE I
ALIGNMENTS
a.k.a random assortment
Duplicated chromosomes randomly tether to spindle
poles
i.e. no set rules for where maternal & paternal
chromosomes should be positioned
Which half of homologous chromosome
pair ends up at which pole is totally
random
223 (8,388,608) possible combos of
FROM GAMETES TO
OFFSPRING
In animals, diploid germ cells
become gametes
Gametes differ from species to
species
MALE GAMETE
FORMATION
Germ cell (spermatogonium) develops into 1°
spermatocyte
Enters meiosis
Results in 4 haploid cells (spermatids) that differentiate
into sperm cells
FEMALE GAMETE
FORMATION
Germ cell (oogonium) develops into 1° oocyte
(immature egg)
Grows in size
4 daughter cells differ in structure & function
When 1° oocyte divides after meiosis I,
one daughter cell (2° oocyte) gets most
of cytoplasm
Other cell (1st polar body) is very small
After meiosis II, one of 2° oocyte’s
daughter cells is 2nd polar body (also very
small)
Other gets most of cytoplasm and develops
into ovum (egg)
1st polar body’s daughter cells are both
polar bodies
Polar bodies eventually degenerate
Sole function: to ensure ovum is haploid
Ovum gets most of cytoplasm & metabolic machinery
Is able to support early cell divisions of new individual
after fertilization
FERTILIZATION: WHEN 2
GAMETES BECOME 1
Male & female gametes unite
Haploid nuclei fuse
Restores diploid nature of cells
(n + n = 2n)
↑ variation among offspring:
•
Random gametes fusing
• Millions of possible chromosome combos in
each gamete
SUMMARY OF MEIOSIS
Nuclear division that halves chromosome number
Results in n male & female gametes that can fuse
during fertilization to produce 2n offspring
CHROMOSOMAL
ABNORMALITIES
Abnormal chromosome structure:
Breakage of chromosome leads to
rearrangements that affect genes on that
chromosome
Abnormal chromosome number:
Chance events occur before or after cell
division that result in wrong chromosome #
CHANGES IN CHROMOSOME
STRUCTURE
Can have neutral to harmful effects, depending
on type of chromosomal change
4 types of rearrangement:
• Inversion
• Deletion
• Duplication
• Translocation
(A) INVERSIONS
Broken fragment reattaches to original chromosome
but in reverse direction
Genes still present in normal #, so less harmful than
other categories
(B) DELETIONS
Fragment of chromosome is lost
Cause severe physical & mental
problems
e.g. cri du chat
(C) DUPLICATIONS
Fragment from one chromosome joins to a sister
chromatid or homologous chromosome
Can have severe effects
(D) TRANSLOCATIONS
Fragment of chromosome attaches to nonhomologous chromosome
May or may not be harmful
If chromosomal changes occur in sperm or egg cells:
= may cause congenital disorders
If chromosomal changes occur in somatic cells:
= can lead to development of cancer
(which is why cancer is generally not heritable)
HERITABLE CHANGES IN
CHROMOSOME #
Chance events occur before or after cell division that
result in wrong chromosome #
Consequences can be minor or lethal
Most changes in chromosome number occur because of
non-disjunction
= 1 pair of chromosomes do not separate during
mitosis or meiosis
Aneuploidy:
Normal # 1 chromosome
e.g. trisomy 21 (Down Syndrome)
Polyploidy:
3n, 4n, etc.
Normal in many plants & animals
# of sex chromosomes can also be abnormal
E.g. XO, XXX, XXY, XYY
Will return to this when covering inheritance