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23 Cards in this Set
- Front
- Back
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What are the features of cell cycle control (6)?
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- a clock or self timer that turns on each event at a specific time
- a mechanism for initiating the events in the correct order - a mechanism to ensure that each event is triggered only once per cycle - binary switches that trigger events in a compete and irreversible fashion - back up systems - availability |
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What are the 3 cell cycle checkpoints?
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1. Start of S
- is the environment favorable? - DNA damage? 2. Start of M - is all DNA replicated? - environment favorable? 3. End of M - check spindle attachment to chromosomes |
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What is the cell cycle control system based on?
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a cyclically activated protein kinase:
cyclin dependent kinase (Cdk) different cyclin-Cdk complexes operate at the major transitions |
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What are Cdks?
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cyclin dependent kinase
Serine/Threonine kinases the original Cdks were cell division cycle (CDC) mutants in yeast (CDC28, cdc2) |
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What are the 4 classes of cyclins and what do they do?
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G1/S
- bind to Cdks at end of G1 - commit cell to DNA replication - levels fall in S-phase S - binding to Cdks is required for the initiation of DNA replication - levels remain high until mitosis M - promotes mitosis and G2/M transition G1 - not found in all cells - help promote passage through START - help govern the activity of G1/S cyclins |
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How does phosphorylation regulate Cdk activity?
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Wee1 kinase adds an inhibitory phosphate.
Cdc25 phosphatase removes the inhibitory phosphate and activates Cdk. |
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What does the binding of CKI do?
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Inhibitor protein binding can also regulate cyclin/Cdk activity
p27 is a Cdk inhibitor (CKI) CKIs function primarily in the G1-S transition |
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The cell cycle control system depends on _______.
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Cyclical proteolysis
degradation |
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Cyclical proteolysis
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Ubiquitin mediated proteolysis is necessary for cyclin
The regulated step in this process is the final addition of ubiquitin to the substrate protein by a ubiquitin protein ligase - SCF: destroys G1-S cyclins and some CKIs to initiate S-phase - APC/C: destroys M cyclins and regulators, initiates M phase |
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ORC
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Origin Recognition Complex
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MPF
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Maturational Promotion Factor
Cdk1/cyclin complex found in frog eggs |
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Is it clock or timer that turns on each event at a specific time regardless of environmental input?
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Both.
- In embryonic cell cycles a simple timer does the job. - In others, more input is needed: a mechanism for initiating events in the correct order, a mechanism to insure that each event is triggered only once per cycle. - These control system usually operate as binary switches that trigger events in a complete and irreversible fashion. Additionally, there are backup systems and feature that adapt to changes |
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How are Cdks activated?
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Cyclin binds and alters the T-loop in Cdk.
The loop moves away from the active site, promoting kinase activity (partial activation). For full activation, Cdk activating kinase "CAK" phosphorylates a Thr in the loop. |
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Explain E1, E2, E3
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A three-part system often used to target proteins for degradation.
E1s: ubiquitin activating enzymes E2s: ubiquitin conjugating enzymes E3s: ubiquitin protein ligases Ub is added to Cys in E1. Then, the Ub is transferred to E2. E3 partners with E2 and adds the Ub to the target protein. |
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ORF
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origin of replication where DNA replication begins
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pre-RC
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In late mitosis and early G1, a complex of initiator proteins
called the prereplicative complex (pre-RC) assembles on the ORF - at S phase, preRC matures into a larger complex called the preinitiation complex, driven by S-Cdks. - Cdks control chromosome duplication through the preRC |
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preinitiation complex
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unwinds DNA and loads the DNA synthesis machinery
preRC matures into this at the S phase |
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ORC
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origin of replication complex
- bound to the origin throughout the cell cycle |
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cohesin
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holds together sister chromatids
called SMCs for Structural Maintenance of Chromosomes |
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activation of M-Cdks
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Activation of M-Cdks begins by the accumulation of the M-cyclins (cyclin B) due to a reduction in degradation
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polo kinase
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phosphorylates cdc25
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How is the APC-Cdc20 complex activated? What does it do?
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kinetochores have to be attached.
it drives chromosome separation. |
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Mad2
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binds to unattached chromosomes... has to do with the APC-Cdc20 complex
(mitotic arrest deficient 2) is an essential spindle checkpoint protein. The spindle checkpoint system is a regulatory system that restrains progression through the metaphase-to-anaphase transition. |
