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cell cycle
regulation of cell behavior to ensure proper function of tissue/organ/organism, dysregulation leads to uncontrolled cell growth
purpose of the cell cycle
division (mitosis), growth and replicating DNA, apoptosis (cell death), development, generation, cells perform tissue specific functions
information that influences cell outcomes
genetic (DNA) and environmental
DNA compaction order
double helix—histone—nucleosome—chromatin—chromosome
histone
protein that DNA is wrapped around
nucleosome
DNA + loop
chromatin
fiber in which nucleosome (DNA + loop) is packaged
chromosome
a structure containing genetic information in the form of genes, (protein + DNA + RNA), forms around time cell divides
sister chromatids
two attached, double-stranded DNA copies of a replicated chromosome. seperate during mitosis and become independent chromosomes
what is necessary for cell division
protein synthesis, organelle production, increased volume of cytoplasm, replicate DNA
interphase
G1, S, G2, prepares cell for cell division
G1 phase
growth phase, cell enters immediately after dividing, chromosome unwinds and uncoils
S
replication phase
G2
prepares cell for cell division by making sure it contains enough proteins and organelles, protein synthesis and organelle production continues
at the end of G2
cell checks for MPF (mitosis promoting factor) protein. if concentration is high, cell exists interphase and enters mitosis
G0
resting phase, comes to this phase if the cell fails G1 checkpoint or doesn’t need to divide, nerve cells and muscle cells spend all of its time here
M phase
mitosis, process by which the cell divides into two identical daughter cells, PMAT
mitosis
division of the cell’s nucleus
cytokinesis
division of the cytoplasm
cell cycle 2 main phases
interphase and cell division (mitosis)
chromosome segregation
two sister chromatids formed, separate from each other and migrate to opposite poles of nucleus, occurs in mitosis, 1 trait
meselsohn-stahl experiment 1
e coli bacteria cells were grown in a medium rich in heavy nitrogen (N-15) to produce radioactively labeled DNA molecules (cell have N-15 in their DNA)
meselsohn-stahl experiment 2
e coli bacteria cells were transferred into a medium with regular N-14 atoms
messelsohn-stahl experiment 3 (key question)
what is the distribution of N-14 and N-15 after consecutive cycles of replication? this question determines if DNA is semi-conserved or not
messelsohn-stahl experiment 4
original parental strands contain N-15 isotopes, replicated daughter strands contained N—14 isotopes, DNA with different densities can be separated by centrifugation
messelsohn-stahl experiment 5
after centrifugation, 3 photographs described band that correlates to DNA molecule that was extracted
density shifts generation after generation, showing DNA is semi-conserved
semi-conservative
1 original strand, 1 new strand, each strand acts as a template for synthesis of a new strand
conservative
original pair, completely new pair
dispersive
2 pairs with old and new DNA dispersed within the DNA
helicase
“unzipping enzyme”, breaks hydrogen bond holding bases together
single-strand DNA-binding proteins
keeps DNA strands separated when unzipped
topoisomerase (DNA gyrase)
keeps DNA from supercoiling by removing the stress caused by unwinding, cuts and reseals DNA
primase
“the initializer”, binds to each one of DNA strands, adds a set of nucleotides (RNA primer) that acts as a signal for DNA polymerase to know where to start to work
dna polymerase III
binds to primer region and adds individual nucleotides 1 by 1 (attaches nucleotides together via phosphodiester bonds), extending synthesized strand (daughter strand)
can only builder new strand in 5’ to 3’ direction
sliding clamp
holds DNA polymerase in place during strand extension
DNA polymerase I
removes RNA and replaces it with DNA, can only build new strand in 5’ to 3’ direction
DNA ligase
“the gluer”, helps “glue” DNA fragments together, seals gap between Okazaki fragments via phosphodiester bonds
DNA replication
synthesizing new strand of DNA from original strand, occurs in nucleus, done before cell divides (mitosis/meiosis)
leading strand
elongates towards the replication fork, synthesized continuously
lagging strand
elongates away from the replication fork, synthesized discontinuously
Okazaki fragment
short sequences of DNA nucleotides synthesized discontinuously and linked together
replication fork
point where unwinding is taking place (can move)
replication origin
a sequence of nucleotides where DNA starts/is initiated
proofreading and mismatch repair
DNA polymerase proofreads the base that has just been added, checks where base pairing it correct
if incorrect base was added: new DNA strand is cut and mispaired nucleotide and its neighbors are removed
DNA polymerase replaces it with correct nucleotides, DNA ligase (glue) seals the gap, increase fidelity (accuracy)
mutation
uncorrected mistakes lead to ___
prophase
DNA condenses from chromatin to chromosomes, 2 centrioles begin to move to opposite ends and synthesize spindles
pro metaphase
nuclear membrane break down allows for spindle attachment to a special region on the centromere, kinetochores (attachment points)
metaphase
centrioles are at opposite ends, spindle fiber attaches to kinetochore and pulls chromosome to the center of the cell (aligns the on the equatorial line)
anaphase
disjunction - separation of chromosomes, spindle fibers pull sister chromatids apart by breaking centromeres and moving chromatids to opposite ends
telophase
nuclear membrane and nucleolus reforms at teach end, spindle begins to deteriorate, chromosomes uncoil and decondense into chromatin
cytokinesis
breaking of the cytoplasm, organelles are distributed among 2 cells, chromosomes have decondensed
chromatin condensation (photo)
-
spindles
protein fibers made from microtubules that are dissasebled into subunits, leading to chromosomal movement
centromeres
holds sister chromatids together
kinetochores
disk shaped proteins on chromatids, spindle fibers attach to it, dissembles microtubules
how does kinetochore dissemble microtubules
motor protein walks kinetochore along microtubules disassembling it into subunits as it passes
microtubules are shortened by disassembly rather than contraction or movement
centrosome
each animal cell has 1, region of the cell that contains 2 identical centrioles
centrioles
synthesize spindle apparatus
experimental evidence of cell cycle control
when a cell in M phase was fused with one in interphase, the nucleus of the interphase cell immediately initiated mitosis, even if its chromosomes had not replicated
general control mechanism
timer, correct sequential initiation of events, binary on/off switches, backup mechanisms, sensors
checkpoints act through ____ signals and are/are not essential for cell progression
negative signals (“who isn’t ready”), are not essential
M-phase promoting factor
combination of cyclin and cdk (cyclin dependent kinase)
protein kinases
enzymes that transfer a phosphate group (usually ATP) onto a target protein, changing protein function from inactive to active
cyclin dependent kinase
catalyzes phosphorylation of other proteins to start M phase, can only phosphorylate proteins when it is bounded with partner cyclin, allosteric activation
cyclins
one of several regulator proteins whose concentrations fluctuate (proteins undergo a cycle of synthesis and degradation) throughout the cell cycle
phosphorylation leads to …
protein being activated, protein being deactivated, or a transferred phosphate group acting as a signal to other proteins to interact with the target protein
ki
kinetic = to move = kinase move
MPF Component Concentration Graph
-
if cyclin is high and cdk is active
cell cycle is on
if cyclin is low/cdk is inactive
cell cycle is off
G1 checkpoint
cell size is adequate, nutrients are sufficient, social signals are present, dna is undamaged
G2 checkpoint
chromosomes replicated successfully, activated MPF is present, dna is undamaged
M checkpoint (metaphase to anaphase)
ensures sister chromatids do not split until all kinetochores are attached properly to the spindle apparatus
M checkpoint (anaphase to telophase)
cells must degrade all of their cyclin and thus turn off MPF activity
enzymes responsible for degrading cyclin are only activated when all the chromosomes have been properly seperated
purpose of all 4 checkpoints
prevent the division of cells that are damaged or that have other problems
what happens if cell cycle checkpoints fail
accumulation of DNA damage, uncontrolled cell growth, genomic instability, loss of apoptosis control, development of genetic disorders
cancer
cells that grow in an uncontrolled fashion, invade nearby tissues, spread to other sites in the body
cancerous cells use nutrients and space needed by normal cells and disrupt function of normal tissues
1st defect cancerous cells have related to cell division
defects that activate proteins required for cell growth when they shouldn’t be active, G1 cyclin is overproduced
2nd defect cancerous cells have related to cell division
defects that prevent tumor suppressor genes from shutting down the cell cycle, p53 (tumor suppressor protein that helps regulate progression) is defective or inactive
malignant tumor
tumor that is actively growing and disrupting local tissues or spreading to other organs
benign tumor
mass of abnormal tissue that develops due to unregulated growth but does not spread to other organs
social control
cells divide in response to signals from other cells, individual cells are allowed to divide when it is in the best interest of the organism as a whole
social control and cancer
normal social controls on G1 checkpoint breakdown in cancerous cells, cells divide in absence of go-ahead signal from growth factors
due to “defect cancerous cells have related to cell division”
p53
tumor suppressant protein, responds to DNA damage and prevents the formation of tumors consequently regulation cell cycle progression, “checkpoint”
p53 abilities
trigger DNA repair, stop cell division, activate apoptosis
p21
an inhibitor of s phase cycling
p53 (1)
p53 is inactive when binded to mdm2
p53 (2)
DNA damage causes phosphorylation of p53
p53 (3)
p53 is phosphorylated and active, mdm2 is removed
p53 (4)
increases the activity of the gene responsible for making p21 protein, “booster that encourages cell to produce more p21”
p53 (5)
p21 binds to cdk2-cylcin complexes and inhbits their activity, leading to cell growth arrest
purpose of meiosis
produce 4 genetically different haploid(n) cells
homologous chromosomes
approximate the same size, same shape, and contain same types of genes in the same locations
gametes
egg or sperm
somatic cells
any cells other than reproductive cells
haploid
(n), having one set of chromosomes
diploid
(2n), having two sets of chromosomes
zygote
cell formed by union of two gametes (an egg and sperm)
karyotype
distinctive appearance of all metaphase or pro metaphase chromosomes, including # of chromosomes, length, and their banding patterns
recombination (crossing over)
exchange of genetic information between non-sister chromatids of homologous chromosomes, produces 2 new recombinant chromosomes