Cell Division Cycle

Cell cycle is duplication and division
Eukaryotic cell cycle usually includes four phases:
- M phase: mitosis and cytokinesis
- Interphase: period between M phases
- S phase: DNA replicates
- G1 and G2: cells grow, monitor internal/external environment for suitable conditions for reproduction
Interphase: Cell continues transcription of genes, synthesizes proteins, and grows
Cell cycle control system ensures cell cycle events occur completely and checks critical points with feedback
G1 to S: control system checks the environment (nutrients and signal molecules) before replicating DNA. Cycle can be arrested in G0 if not suitable.
G2 to M: undamaged DNA is confirmed to be fully replicated prior to mitosis (if intact DNA, cell enters mitosis). Cell cycle control machinery checks duplicated chromosomes are attached to the mitotic spindle before being pulled apart.
Cell cycle control system works to turn machinery on and off for new components
Cyclically activated protein kinases (Cdks) are key to activating and inactivating proteins/complexes for mitosis, based on de/phosphorylation of proteins
Protein Kinases are involved in transitioning phases G1 to S and another before M to mitosis
Cyclins are proteins in the control system switching kinases on/off
Cyclins are not enzymatic but bind to cell cycle kinases, activating them
Cyclin-dependent kinases (Cdks): kinases of cell cycle control systems

Different Cyclin-Cdk complexes trigger different steps in the cell cycle
- M-cyclin: acts in G2 and triggers M phase (forms M-Cdk)
- S-cyclin and G1/S cyclin: bind to certain Cdk proteins in late G1 to form S-Cdk
Cyclin concentrations regulated by transcription and proteolysis
- Increased gradually by transcription of cyclin genes
- Rapidly decreased via targeted destruction of the protein
- Anaphase-promoting complex (APC) degrades M and S cyclins part way through M phase, tagging cyclins with ubiquitin, leading to degradation by proteasomes
Cdk activity can be blocked by Cdk inhibitor proteins
Some may help Cdks remain inactive during G1

Metabolic activity, cell growth and repair, uses IC and EC signals
Cdks are stably inactivated in G1
If S and M-Cdks are active, the cell will immediately replicate DNA and divide without sufficient time in G1 or G2
Mitogens promote production of cyclins that stimulate cell division
Mitogens are signals from other cells

S-Cdk initiates DNA replication and blocks re-replication
- Occurs in G1 with preparation for DNA replication: Proteins recruiting to sites along chromosomes (origins of replication) is recruited by ORC
- Origin Recognition Complex (ORC)- top of replication origins
Replication signal from S-Cdk helps start DNA replication, activating helicases and assembling proteins at replication fork
S-Cdk inhibits re-replication

Cell recognizes components and distributes equally into 2 daughter cells
M-Cdk allows for arrangement in early stages of mitosis
- Helps prepare duplicated chromosomes for segregation
- Induces mitotic spindle assembly
- M-Cdk complexes accumulate through G2, then activated when its inhibitory phosphate is removed by Cdc25 at the end of G2. Activated complex can trigger addition M-Cdk complexes
Cohesins: hold duplicated chromosomes together during DNA replication
Condensins: condense duplicated chromosomes so they can be easily segregated
Spindle fibers (microtubules) are part of the mitotic spindle
Sister chromatids are held together by cohesins
Mitotic spindles composed of microtubules (MTs) and MT-associated motor proteins
- Pull duplicated chromosome copy to each daughter cell
Centrosomes in animal cells duplicate and start to assemble mitotic spindles; Duplicated chromosomes are attached to mitotic spindle, align at an equator, to form metaphase plate.
Proteolysis (separation of sister chromatids at anaphase) is triggered by separase, held inactive by securin, which is targeted by APC (anaphase promoting complex), which allows separase to detach duplicated sister chromatids and distribute them into opposite daughter cells
Mitotic spindle assembly is dictated by spindle assembly checkpoint, controlling the onset of anaphase and exit from mitosis

Cytoplasm is split between daughter cells
Mitotic spindle determines the plane of cytoplasmic cleavage
Contractile ring of animal cells made by actin and myosin filaments
Cytokinesis in plant cells involves formation of new cell wall (phragmoplast) from remains of interpolar MTs.
Membrane-enclosed organelles are distributed randomly to daughter cells during division

Cell death, regulated by an intracellular proteolytic cascade.
Caspases (proteases) are important in apoptosis
Inherent to cell until signaled
Intrinsic death pathway involves proteins in the Bcl2 family regulating caspase activation
Bax and Bak induce cell death
Extracellular signals can induce apoptosis by activating death receptors (like Fas)
Extracellular signals controlling survival, growth, and division
Survival factors inhibit apoptosis and promote cell survival (through pathways relating to Bcl2 proteins)
Mitogens promote cell division, overcoming inhibitory mechanisms, through S phase of cell cycle
Growth factors stimulate cell growth by increasing protein/macromolecular synthesis rates (and decreasing rates of degradation).