Post on 19-Jan-2016
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
2
What does cell cycle mean?
An ordered series of events leading to cell replication
3
Cell Cycle Control
Control of cell division is vital
4
Cell Cycle Control
Cells should divide where and when needed
Nearly identical proteins regulate in all eukaryotes
5
Cell cycle
6
2 key molecular processes in the cell cycle
7
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
8
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)
9
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
10
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.
11
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.
12
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
13
14
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
15
The Concentrations of The Three Major Cyclins
16
Regulators of Cyclin-CDK Activity
Kinases and PhosphatasesCAK kinase
Wee1 kinase
Cdc25 phosphatase
Inhibitory Proteinsp27
INK4
Rb
Ubiquitin-Protein LigasesSCF
APC/C
17
Kinases and Phosphatases
18
Inhibitory Proteins
19
Ubiquitin-Protein Ligases
20
Ubiquitin-Protein Ligases
21 Control of the G1-S phase transition
Growth Factor
22
23
An Overview of the Cell-cycle Control System
24
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
27
28
Meiosis
Meiosis phases