Mitosis and Cell Cycle 1 and 2 Flashcards
goal of somatic cell cycle
produce two cells (geneticaly) identical to the first cell
four phases of cell cycle
G1 S G2 M
S phase
synthesis
M phase
mitosis
segregation of material duplicated in S phase
G1 and G2 phases
gap phases
cycle regulation of subsequent phase
G0
resting phase before G1 (quiescent state)
Interphase
all phases except mitosis
G1, S, and G2
restriction point
forces commitment to synthesis through G1 phase
size homeostasis
cell growth must complement cell division
goes away in embryo, cells get smaller as they divide
cyclin-dependent kinase (CDK)
protein kinase that takes gamma phosphate from ATP and adds it to residues to regulate activity (serine, threonine, and tyrosine)
CDK only does serine/threonine
phosphorylation action
either activates or inhibits activity
CDK subunits
monomeric Cdk is inactive, always present in cell
cyclin subunit activates Cdk (variably present)
G0 cell phase has no cyclin
cyclin
different cyclins exist at different points in the cell cycle to drive different activities
growth factor GF
pushes cell from G0 to G1
inhibitors
negative regulation
inhibit inhibitor
turn off deregulation to get up regulation
RB
inhibitor to entering cell cycle
CDK cycle
CDK 2, 4, and 6 interact with different kinases to perform different functions in the cell cycleRB
Rb (Retinoblastoma protein) Regulation
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CDI
CDK Inhibitors
CDI action
bind to CDK/cyclin complex to inhibit action
CDI relevance to cancer
frequently mutated, p16 missing in melanoma
p53 mutated in almost half of all cancers
meaning of the numbers in protein names
weight in kD, i.e. p27 means the 27kD p protein
cancer action of inhibitors
failed inhibitor leads to overexpression of a regulated protein
origin of replication
site on chromosome where replication begins
~100k in human genome, not uniformly distributed
okazaki fragments
lagging strand DNA segments synthesized from lots of RNA primers
how do you get faster DNA replication
use more replication origins (i.e., rapid growth cell types, embryos)
reinitiation
using the same origin twice in one cycle, never seen, would lead to an extra chromosome
Orc
Origin recognizing complex
Orc1-6
gloms onto DNA at origin, becomes a “landing pad” for Cdt1 and Cdc6, brings in hexomeric complex DNA helicase (Mcm2-7)
cell cycle checkpoints
size?
Make DNA?
New DNA?
Spindle?
defective checkpoints
cancerous cell growth
hodgkins lymphoma
secondary cancer from original treatment
DNA checkpoint regulation
monitor DNA for damage or block replication entirely
DNA Damage regulator
Rad17 binds to DNA damage
sends a signal to ATM and ATR to block P53/p21
P53/p21
inhibit CDK in DNA damage regulatory steps
inhibits all in cyclin dependent kinase activity in cell
Types of DNA checkpoint mechanisms
Double strand breaks
stalled replication forks
DNA mismatches
nucleotide damage
folate function
needed for making nucleotides
not enough folate leads to poor DNA replication
BRCA2
tumor suppressor, senses DNA damage and blocks cell cycle
missing one copy in the 5% of women getting breast cancer (checkpoint mechanism)
cancer cell achilles heel
inherent instability of cell due to checkpoint failures
crossover during mitosis
infrequent, not for reorganization of genetic material, but a tool for DNA repair
crossover during meiosis
frequent (1000x mitosis), for genetic recombination
