J a v a d J a m s h i d i

F a s a U n i v e r s i t y o f M e d i c a l S c i e n c e s , D e c e m b e r 2 0 1 5

The Eukaryotic

Cell Cycle

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What does cell cycle mean?

An ordered series of events leading to cell replication

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Cell Cycle Control

Control of cell division is vital

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Cell Cycle Control

Cells should divide where and when needed

Nearly identical proteins regulate in all eukaryotes

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Cell cycle

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2 key molecular processes in the cell cycle

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Cell cycle Timing

The progression of cell cycle stages is the same for all eukaryotes

Rapidly replicating human cells the full cell cycle in about 24 hoursG1 takes 9 hours The S phase 10 hours G2, 4.5 hours Mitosis 30 minutes

90 minutes in rapidly growing yeast cells.

Only 8 minutes in early embryonic development of the fruit fly

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Cyclins and CDKs

The master controllers of the cell cycle

Protein kinases that contain a:

Regulatory subunit (cyclin)

Catalytic subunit (cyclin-dependent kinase, or CDK)

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Cyclins and CDKsRegulate the activities of multiple proteins involved in:

Entry into the cell cycleDNA replicationMitosis

By phosphorylating them at specific regulatory sites

Activating some

Inhibiting others

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Three key features of CDKs

Only active when bound to a regulatory cyclin subunit

Different types of cyclin-CDK complexes initiate different event

G1 CDKs and G1/S phase CDKs promote entry into the cell cycle S phase CDKs trigger S phaseMitotic CDKs initiate the events of mitosis

Multiple mechanisms are in place to ensure that the different CDKs are only active in the specific stages of the cell cycle.

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Three key features of Cyclins

Cyclins bind to and activate CDKs, define their activity and substrate specificity

Cyclins are only present during the cell cycle stage that they trigger and are absent in other cell cycle stages.

Cyclins not only regulate a particular cell cycle stage but also prepare for the next cell cycle stage.

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Key Principles Govern the Cell Cycle

Cell cycle events must occur in the proper order

These oscillations in CDK activity are a fundamental aspect of eukaryotic cell cycle control

Positive feedbacksNegative feedbacks

The surveillance mechanisms which called checkpoint pathways

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Cyclins and CDKs: Nomenclature and Their Roles in the Mammalian Cell Cycle

CDK Cyclin FunctionGeneral Name

CDK1 Cyclin A and B Mitosis Mitotic CDKs

CDK2 Cyclin E and A

Entry into the cell cycleS phase

G/S phase CDKsS phase CDKs

CDK4 and CDK6 Cyclin D

G1Entry into the cell cycle

G1 CDKs

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The Concentrations of The Three Major Cyclins

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Regulators of Cyclin-CDK Activity

Kinases and PhosphatasesCAK kinase

Wee1 kinase

Cdc25 phosphatase

Inhibitory Proteinsp27

INK4

Rb

Ubiquitin-Protein LigasesSCF

APC/C

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Kinases and Phosphatases

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Inhibitory Proteins

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Ubiquitin-Protein Ligases

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Ubiquitin-Protein Ligases

21 Control of the G1-S phase transition

Growth Factor

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An Overview of the Cell-cycle Control System

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DNA Replication in S phase

Eukaryotic chromosomes are replicated from multiple replication origins

No eukaryotic origin initiates more than once per S phase

S phase continues until replication from all origins along the length of each chromosome are completed

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Meiosis

Meiosis phases