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Cell Division (Mitosis and Meiosis)

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what are the phases of the cell cycle?
G1
S
G2
M
what phases does Interphase consist of?
G1
S
G2
what phases does mitosis consist of?
Prophase, Prometaphase, Metaphase, Anaphase, Telophase, Karyokinesis, Cytokinesis
when does G1 start?
end of mitosis
why is G1 the longest phase?
cell growth: gather nutrients, synthesize RNA and proteins
what are the two checkpoints in G1?
G1 DNA-damage checkpoint
-monitor integrity of newly replicated DNA

G1 Restriction checkpoint
-the point of no return
-mediated by Rb
-evaluate replication potential for S phase
what are the two phases of S?
synthesis and checkpoint
what happens during synthesis of S phase?
DNA replication
what happens during checkpoint at end of S phase?
S DNA-damage checkpoint
-check quality of newly replicated DNA
what are the three phases of G2?
G2 phase
-cell prepares for division

2 checkpoints
what are the two checkpoints of G2 phase?
1. unreplicated DNA checkpoint
-prevents progression into mitosis before completion of DNA synthesis

2. DNA-damage checkpoint
-monitor integrity of newly replicated DNA
what are the two checkpoints of the M phase?
1. spindle-assembly checkpoint
-make sure all chromosomes, spindles, kinetochores are attached
-prevents premature entry into anaphase

2. chromosome segregation checkpoing
-prevents cytokinesis until full separation of chromsomes
what is the kinetochore?
-large protein complex
-forms near centromere
-attaches chromosome to mitotic spindle
what are centrosomes?
-hollow, rigid cytoskeleton structure with alpha and beta subunits
what is the microtubule organizing center?
contains a pair of centrioles at the poles
what does the mitotic spindle consist of?
centrosomes + microtubules + motor proteins
which way does dynein move?
towards negative end
which way does kinesin move?
towards positive end
what happens during Interphase?
G2 -> M transition

-centrosomes separate
-centrosomes move to opposite poles
-orientation of spindles determines cell's plane of division
what happens during Prophase?
-condensation of replicated chromosomes
-chromatids connected at centromere
-kinetochores form near centrosomes
-mitotic spindle assembly
-nucleolus disassembles
what happens during Prometaphase?
-breakdown of nuclear envelope (dissolution of nuclear lamina)
-spindle microtubules bind to kinetochores
what happens during Metaphase?
-chromosomes align at equatorial, metaphase plate
-kinetochore microtubules attach sister chromatids to opposite poles
-motor proteins move chromatids into position
what happens during Anaphase?
-anaphase promoting complex (APC)
--> cleavage of chromatids
-sister chromatids separate
--> each pulled to opposite spindle poles by dyneins
what is anaphase A?
kinetochore microtubules get shorter
what is anaphase B?
-overlap microtubules lengthen
-spindle poles move apart
what happens during Telophase?
-sister chromatids arrive at opposite poles and decondense
-nuclear envelope reassembly
-assembly of contractile ring
in what phase is karyokinesis? how does the cell look?
telophase

one cell with two distinct nuclei
what happens during Cytokinesis?
-cleavage furrow
-separation due to contractile ring
-creation of 2, genetically identical, diploid 2n daughter cells
-completion of cell cycle
what is the contractile ring?
separates cytoplasm during cytokinesis; actin and myosin II
what are the regulators during G1?
cyclin D, Cdk 4/6
phosphorylation of Rb
p53
what are the regulators during S?
cyclins E and A, Cdk 2
what are the regulators during G2?
cyclin A, Cdk 1
what are the regulators during M?
cyclin B, Cdk 1
APC
explain the regulation of retinoblastoma protein Rb?
in resting cells of G1, Rb is active (hypophosphorylated)
--> binds E2F and is an inhibitor of cell cycle progression

in G1 -> S, Rb is inactive (hyperphosphorylation)
--> due to increased cyclin D, Cdk 4/6 activity, Rb dissociates from E2F (which is now free to activate gene expression)
what happens during G2 to M progression?
CdC 25 phosphatase removes inhibitory phosphorylatin of Cdk1 so Cdk1 can bind to cyclin B; this complex activates mitosis
what are two roles of p53?
1. apoptosis
2. cell cycle regulation during G1 phase
what does p53 do during cell cycle regulation?
stimulates transcription of Cdk inhibitory proteins
what is the phase of anaphase promoting complex?
to separate sister chromatids
-degradation of securing
-activation of separate
-cleavage of cohesin complexes

degradation of M phase cyclin B
what are the proteins involved in G1 DNA Damage checkpoint?
p53 activation
p21 activation (Cdk inhibitor)
what are the proteins involved in S DNA Damage checkpoint?
BRCA1 activation (repairs double stranded DNA breaks)
what are the proteins involved in G2 DNA Damage checkpoint?
Cdc25 inactivation
what are tumor suppressor genes?
-genes that maintain normal cell growth
-prevent unregulated cell cycle progression
-loss of function mutations enhance susceptibility to cancer
how are cancer cells regulated?
-no cell cycle arrest (lack of p53)
-cell division with damaged DNA
-continued mutation, selection, and tumor progression
-increased genetic instability
what are protooncogenes?
genes whose protein products control cell growth, proliferation, and differentiation
what are oncogenes?
mutated protooncogenes
what are the 4 stages of Prophase I in Meiosis?
1. leptotene
2. zygotene
3. pachytene
4. diplotene
what happens during leptotene?
-chromatin condensation
-sister chromatids condense and connect to each other
-pairing of homologous maternal/paternal chromosomes beings
what happens during zygotene?
-synapsis (synaptonemal complex binds chromosomes together)
what happens during pachytene?
synaptonemal complex complete and over
what happens during diplotene?
-synaptonemal complex begins to break down
-homologous chromosomes begin to separate
-chiasmata (newly formed junctions between chromosomes)
what happens during Metaphase I in Meiosis?
1. homologous chromosomes randomly align on equatorial plate at chiasmata
2. spindle microtubules attach to kinetochores
what happens during Anaphase I in Meiosis?
homologous maternal/paternal chromosomes pulled to opposite sides
what are the differences between Meiosis II and Mitosis?
-no DNA replication
-no crossover
-2nd meiotic division separates sister chromatids
-number of chromosomes in haploid gametes half the number of diploid parent
why don't we want errors in cell division?
increase in genetic instability
what does non-disjunction cause?
aneuploidy (improper separation during anaphase)
what are 4 types of chromosome damage or fragmentation?
-deletion
-insertion
-inversion (fragment reattaches to same chromosome but reversed)
-duplication (fragment treated as a separate chromosome)
what is polyploidy?
more than 2 sets of chromosomes (i.e. 3n, 4n etc)