The Cell Cycle Chromosomes duplicated and segregated into two genetically identical cells

Phases Of The Cell Cycle S phase: DNA synthesis M phase: nuclear and cytoplasmic division G 1, G 2 : gaps, monitor internal and external conditions

Morphological Changes During Cell Cycle In metaphase replicated chromosomes aligned at equator At anaphase sister chromosomes move to opposite poles

Control Of Cell Cycle System triggers series of events in correct order Checkpoints: arrest cell cycle if previous events not completed or environment unfavorable

Cyclin-Dependent Kinases Cdks active when bound to cyclin Cyclin-Cdk complexes promote passage through particular stages Cyclins undergo cycles of synthesis and degradation

Activating phosphorylation- requires activating kinase Inhibitory phosphorylation- inhibitory kinase, removed by phosphatase Regulation Of Cdk Activity By Phosphorylation

Regulation Of Cdk Activity By Cdk Inhibitor Proteins Inhibit activity of cyclin-Cdk complex Prevent association of Cdk with cyclin

Proteolysis of Cyclins Cyclin degradation by transfer of ubiquitin Mediated by ubiquitin ligases acting at particular stages APC/C degrades M cyclins

Initiation Of DNA Replication S-cyclin-Cdk phosphorylates ORC for DNA replication to begin Re-replication prevented by Cdc6 phosphorylation and inhibition by geminin

Early Events Of Mitosis M-cyclin-Cdk phosphorylation of: Nuclear lamins Protein complex that mediates chromosome condensation Proteins that regulate microtubules

Triggered by APC/C ubiquitin ligase APC/C targets degradation of separase inhibitor, resulting in cleavage of chromatid cohesion complex Anaphase

Exit From Mitosis Chromosomes decondense, spindle disassembles, nuclear envelope reforms Requires degradation of M-cyclin by APC/C-mediated ubiquitylation

Control Of G 1 Progression By Retinoblastoma Protein G 1 -cyclin-Cdk phosphorylates Rb, resulting in release of E2F and transcription of S phase genes

Mitogen Stimulation Extracellular signals that stimulate G 1 - and G 1 /S-cyclin-Cdks

Checkpoint Mechanisms –DNA replication checkpoint: blocks G 2 →M –DNA damage checkpoint: blocks G 2 →M Mediated by Cdc25 phosphatase –DNA damage checkpoint: blocks G 1 →S Mediated by p53

DNA damage activates p53, which turns on p21 Cdk inhibitor DNA Damage Checkpoint by p53

Mechanics Of M Phase Chromosomes condense Mitotic spindle forms Nuclear envelope breaks down Chromosomes attach to spindle microtubules

Sister chromatids move to opposite poles Chromosomes aligned at equator

Chromosomes at poles Nuclear envelope reforms Contractile ring of actin and myosin pinches cell in two

Three classes: kinetochore, overlap, astral Participate in movement of chromosomes Classes Of Spindle Microtubules

Anaphase A: chromosome movement toward poles by kinetochore MT shortening Anaphase B: separation of poles by motor proteins and overlap MT elongation Movement At Anaphase

Forces at Anaphase A Kinetochore microtubule depolymerization Microtubule flux: prior to anaphase, tension generated from balanced tubulin addition (+), removal (-)

Pushing by plus end directed motors Pulling by minus end directed motors Motor Proteins In Anaphase B