1. cell cycle
1.1. interphase
1.1.1. most time spent in this stage
1.1.1.1. cellular content continously synthesised
1.1.1.2. amount of nuclear DNA doubles
1.1.2. G0
1.1.2.1. if conditions are not optimal for cell growth
1.1.2.2. cells that become arrested at G1 waiting for a signal to reenter cell cycle + commit to divide
1.1.3. G1 phase
1.1.3.1. growth and biosynthesis
1.1.3.2. major decision as to if and when cell undergoes cell division again
1.1.3.2.1. G0
1.1.3.2.2. terminal differentiation
1.1.3.2.3. arrest can also happen in G2
1.1.3.3. time gap that separates S phase from preceding M phase
1.1.3.4. time variable depending on cell type
1.1.3.4.1. typical G1=8-10hrs
1.1.3.4.2. some spend few mins/hrs where other are delayed for a long time
1.1.4. S phase
1.1.4.1. DNA replication
1.1.4.1.1. copying of chromosomes
1.1.4.2. new nuclear DNA is synthesized
1.1.4.2.1. 2 copies of each chromosomal DNA is made
1.1.4.3. mammalian cells
1.1.4.3.1. 6-8hrs
1.1.5. G2 phase
1.1.5.1. further growth
1.1.5.2. separates the end of S phase from the onset of the next Mphase
1.1.5.3. more uniform duration than G1
1.1.5.3.1. 4-6 hrs
1.1.5.4. shorter than G1
1.1.5.5. final preparations made for onset of mitosis
1.1.5.6. end of G2
1.1.5.6.1. chromosomes start to condense from extended form>compact extensively folded structures
1.1.5.6.2. uncompacted form
1.2. M-phase
1.2.1. mitosis (nuclear division)
1.2.1.1. 5 stages
1.2.1.1.1. Prophase
1.2.1.1.2. prometaphase /late prophase
1.2.1.1.3. metaphase
1.2.1.1.4. anaphase
1.2.1.1.5. telophase
1.2.1.1.6. anagram
1.2.1.1.7. purpose of mitosis
1.2.2. cytokinesis (cytoplasmic division)
1.2.2.1. animals
1.2.2.1.1. cleavage burrow
1.2.2.2. plants
1.2.2.2.1. cell plate
1.2.2.2.2. have a rigid cell wall
1.2.2.3. cells separate
1.2.2.3.1. cytoplasm is divided into two
2. cell cycle control
2.1. progression through cell cycle is regulated
2.1.1. key transition points
2.1.1.1. signals received
2.1.1.1.1. internal conditions
2.1.1.1.2. external conditions
2.1.1.2. 3 control points
2.1.1.2.1. Restriction point(start)
2.1.1.2.2. G2-M boundary
2.1.1.2.3. Metaphase-Anaphase transition
2.1.2. control system must
2.1.2.1. ensure that events associated with each phase of cell cycle are carried out at the appropriate time and in appropriate sequence
2.1.2.2. ensure that each phase of the cycle has been properly completed b4 going on to the next
2.1.2.3. be able to respond to external conditions that indicate need for cell proliferation
2.1.2.3.1. quantity of nutrients available/presence of growth signalling molecules
2.2. regulation
2.2.1. G0 phase
2.2.1.1. if conditions not optimal
2.2.1.1.1. cells stay here until conditions improve
2.2.2. regulatory proteins
2.2.2.1. find them using models
2.2.2.1.1. oocyte growth and egg cleavage in Xenopus
2.2.2.1.2. yeast mutants
2.2.2.1.3. Cdc sensitive mutants
2.2.2.1.4. cell fusion experiments 1970s
3. overview of cell division
3.1. meiosis
3.1.1. haploid cells
3.1.2. genetic variation introduced
3.1.2.1. genetically different gametes produced
3.1.3. random assortment of chromosomes
3.2. mitosis
3.2.1. asexual
3.2.2. diploid
3.2.2.1. homologous chromosomes copies
3.2.2.2. one from mom
3.2.2.3. one from dad
3.2.3. produce genetically identical daughter cells
3.3. cell growth accompanied by cell division
3.3.1. cell division
3.3.1.1. one cell gives rise to 2 new daughter nuclei
3.4. single celled organisms
3.4.1. cell division increases total # of individuals in pop.
3.5. multicellular organisms
3.5.1. cell division
3.5.1.1. increases # of cells
3.5.1.1.1. growth of organism
3.5.1.2. replaces cells that have died
3.6. cell cycle
3.6.1. a series of discrete stages that a cell passes through
3.6.2. begins
3.6.2.1. 2 new cells are formed from a division of a single parental cell
3.6.3. ends
3.6.3.1. one of these cells divides again into 2 cells
3.6.4. Mphase
3.6.4.1. division process-mitotic phase
3.6.4.1.1. point in cycle when cell actually divides
3.6.4.1.2. 2 overlapping events
3.6.4.1.3. most visually distinctive
3.6.4.1.4. lasts >1hr(30-45mins)
3.6.5. generation time
3.6.5.1. overall length of cell cycle
3.6.5.2. in mammalian cells
3.6.5.2.1. 18-24 hrs
4. cell cycle control system
4.1. operates like a timer/oscillator that triggers the events of the cell cycle in a set sequence
4.2. triggers the essential processes of the cell cycle
4.2.1. DNA replication,mitosis,cytokinesis
4.3. info about completion of cycle events and signals from the environment an cause control system to arrest cycle at checkpoints
4.4. system of biochemical switches
4.4.1. initiate specific cell cycle events
4.4.2. role
4.4.2.1. increase efficiency and reliability of cell cycle progression
4.4.3. features
4.4.3.1. binary (on/off)
4.4.3.1.1. launch events in compete irreversible fashion
4.4.3.2. robust and reliable
4.4.3.2.1. backup mechanisms and other features allow the system to operate effectively under variety of conditions
4.4.3.3. highly adaptable
4.4.3.3.1. can be modified to suit specific cell types
4.4.3.3.2. modified to respond to specific i.c/e.c. signals
4.5. 3 major checkpoints
4.5.1. Restriction point/Start
4.5.1.1. cell commits to cell cycle entry and chromosome duplication
4.5.1.2. late G1
4.5.2. G2/M checkpoint
4.5.2.1. control system triggers early mitotic events
4.5.2.1.1. chromosome alignment on spindle of metaphase
4.5.3. metaphase/anaphase transition
4.5.3.1. control system stimulates sister chromatid separation
4.5.3.1.1. completion of mitosis and cytokinesis
4.5.4. control system blocks progression through each of these checkpoints if it detects problems inside/outside of the cell
4.5.5. Start/restriction point
4.6. central components of the cell cycle control system
4.6.1. cyclin dependent kinases(Cdks)
4.6.1.1. family of protein kinases
4.6.1.2. activities rise and fall as cell progresses through cycle
4.6.1.2.1. cyclical changes in phosphorylation of intracellular proteins that initiate/regulate major events of the cell cycle
4.6.1.2.2. increase in activity at G2/M checkpoint
4.6.1.3. cyclical changes in Cdk activity are controlled by Cdk regulators
4.6.1.4. levels are constant in each cell cycle
4.6.1.5. Cdk regulators
4.6.1.5.1. complex array of enzymes and other proteins that regulate kinases
4.6.1.5.2. most important=cyclins
4.6.1.6. suppression of cdk activity
4.6.1.6.1. Wee1 protein kinase
4.6.1.6.2. Cdk inhibitor proteins ( CKIs)
4.7. overview of cell cycle control system
4.7.1. core of cell cycle control system
4.7.1.1. series of cyclin-Cdk complexes
4.7.1.1.1. activity of each complex is influenced by various inhibitory mechanisms
5. Growth Factors and cell proliferation
5.1. mammalian cells become arrested in G1 in absence of growth factors
5.2. stimulatory growth factors
5.2.1. trigger growth and division
5.2.2. found in blood serum
5.2.3. e.g. PDGF (platelet-derived growth factor)
5.2.3.1. a protein produced by blood platelets that stimulates the proliferation of connective tissue cells and smooth muscle
5.2.3.2. acts as a mitogen
5.2.3.2.1. stimulatory extracellular signals that stimulate cell division in animal cells
5.2.3.3. discovery
5.2.3.3.1. fibroblasts in a culture dish proliferate when provided with serum but not when provided with plasma
5.2.3.3.2. blood clot=platelets in clot releasing contents of secretory vesicle
5.2.3.4. helps stimulate cell division during wound healing
5.3. density dependent inhibition and anchorage dependence
5.3.1. when mammalian cells are cultured in a dish in presence of serum
5.3.2. adhere to bottom of dish
5.3.2.1. anchorage dependence
5.3.3. spread out and divide until they form a confluent monolayer
5.3.4. each cell is attached to the dish and contacts its neighbours on all sides
5.3.5. normal cell stops proliferating when monolayer reached
5.3.5.1. due to competition for mitogens
5.3.6. cell proliferation in normal cells depends on availability of mitogens,growth factors and survival factors
5.3.7. cancer cells
5.3.7.1. dont exhibit density dependent inhibition or anchorage dependence
5.4. extracellular signal molecules
5.4.1. regulate cell size and cell number
5.4.2. 3 classes
5.4.2.1. mitogens
5.4.2.1.1. stimulate cell division by triggering a wave of G1/S-ck activity
5.4.2.2. growth facotrs
5.4.2.2.1. stimulate cell growth(^ in size)
5.4.2.3. survival factors
5.4.2.3.1. promote cell survival by suppressing apoptosis