Poster die een overzicht geeft van de belangrijkste enzymen betrokken bij de cel cyclus. Daarnaast geeft het ook informatie over de checkpoints, checkpoint control mechanisms, ORI licencing, mitotic spindle formation, etc.
General CDK regulation: Cdc14 (humans TAZ) is a phosphatase that removes
Activating phosphorylation Inhibitory phosphorylation (these two necessary for M phase entrance in S. Pombe When no microtubuli attached to kinetocores: APC-Mad2 Cdh1 phosphate active Cdh1
securin-UB inhibition Cdh1-APC complex formation ubiquitylation of cyclin B (neccesity for M phase exit!)
CAK kinase stimulated by Wee1 reversed by Cdc25 (phosphatase) When microtubuli: APC free to bind Cdc20
Kleisin = Cohesin Cyclin B destruction surplus phosphatase (Cdc14 mainly) activity
Dephosphorylation of targets that caused mitotic preparation in prophase
Exit from of telophase: cytokinesis, retraction of microtubuli
Unlicensed ORIs Entrance of G1 phase
• G2/M phase (except telophase)
• Cdc6, Ctd1 phosphorylated by cyclin B-
CDK no MCM loading
Meta to anaphase transition
During prophase, Telophase to G1 transition
Cyclin B phosphorylates E3 Aka ‘mitotic exit network’
ubiquitine ligase
Ubiquitilation cyclin B itself: Spindle-assembly checkpoint
inactivation • Anaphase entry
Negative feedback loop Spindle-position checkpoint
• Telophase entry Exit of the G0 phase
• Addition of growth factors Via c-Jun, c-Myc, Fos signals gene transcription
G2 to M-phase transition CDK2 transcribed (activity controlled by p27 and p21) p21 under p53 stim
ORI licencing
• Leads to transcription of E2F and
DNA damage checkpoint 4 • Late telophase, early G1
During G0:
• M phase entry • Low cyclin B activity due to
• No CDKs or cyclins produced
ubiquitylation by formed
Mitotic cyclin-CDKs Cdh1-APC complex
Intra S-phase checkpoint • Cyclin A-CDK1 • Unphosphorylated Cdc6 and
• M phase entry • Cyclin B-CDK2 CD1 can be loaded
(major) • Loading MCM to ORC possible
= license
Mid-G1 to late-G1 to S transition
INK4 family: CKI specific for G1
Mid-G1 cyclin-CDKs Cyclin D inhibition by antigrowt
• Cyclin D-CDK4
CIP family of CKI’s active in S/G2/M • Cyclin D-CDK6
• P21: DNA damage response
• P27:
• p57
DNA damage checkpoint 1
• G1 phase
Late-G1 cyclin-CDKs
• Cyclin E-CDK2
S-phase cyclin-CDKs
• Cyclin A-CDK2
Cell signalling cascades
DNA damage checkpoint 3
• S phase G1 to S transition: passage through restriction
DNA damage checkpoint 2 point (yeast, similar to INK4s in mammals)
Unlicensed ORIs • S phase entry
• Fired ORI’s have no MCM complex and
cannot load these because assembly of G1 cyclin:
Cdc6 and Cdh1 that has to happen first is
not possible, as these are already
phosphorylated by the first firing.
• Free Cdc6 and Cdh1 is not a target of cyclin
A-CDK2
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