Cell Cycle Flashcards
At the end of ___, cell scans the extracellular environment to see if it’s okay to proceed. This is known as a ___ ___. If the cells do not pass this point, they enter into __.
At the end of G1, cell scans the extracellular environment to see if it’s okay to proceed. This is known as a RESTRICTION POINT. If the cells do not pass this point, they enter into G0.
Cdks can only phosphorylate targets when they are bound to ____.
Cdks can only phosphorylate targets when they are bound to CYCLINS.
The 4 Classes of Cdks G1 Cdk: promotes \_\_\_\_\_\_ \_\_\_\_ \_\_\_\_ \_\_\_\_ \_\_\_\_\_ G1/S Cdk: commits cell to \_\_\_\_ S Cdk: Initiates \_\_\_\_\_ M Cdk: promotes \_\_\_\_
The 4 Classes of Cdks G1 Cdk: promotes PASSAGE THROUGH RESTRICTION POINT G1/S Cdk: commits cell to REPLICATION S Cdk: Initiates REPLICATION M Cdk: promotes MITOSIS
Replication Initiation:
- ____, a large, multi-protein complex binds to origins of replication and act as _____ for other ____ ____ to initiate replication at different positions throughout the genome so that ____ ____ is duplicated.
- After binding of ___, ___ is recruited, which recruits ____, together, they form the ____.
-Then, ___ triggers S-phase by _____ the ____ and ____ (for degradation).
Replication Initiation:
- ORC, a large, multi-protein complex binds to origins of replication and act as LANDING PAD for other REGULATORY PROTEINS to initiate replication at different positions throughout the genome so that ENTIRE GENOME is duplicated.
- After binding of ORC, CDC6 is recruited, which recruits MCM, together, they form the PRE-RC.
-Then, S-CDK triggers S-phase by PHOSPHORYLATING the ORC and CDC6 (for degradation).
How is initiation of replication or entry into S Phase controlled?
- ____ is usually present at low levels throughout the cell cycle but increases transiently in ___.
- ____ then binds ORCs, which recruits ____ helicases.
- In sum, ___ functions to have the Pre-RC poised to replicate DNA.
-Meanwhile, _____ transcription is activated in late G1, and ___-____ complex forms activating _____ that then phosphorylates ____ and assemble the ____ + other machinery at the origin, while also activating _____.
- _____ also prevents re-replication because it phosphorylates _____ for degradation once the ORC has fired for replication.
- _____ also phosphorylated _____ and causes their export from nucleus.
How is initiation of replication or entry into S Phase controlled?
- CDC6 is usually present at low levels throughout the cell cycle but increases transiently in G1.
- CDC6 then binds ORCs, which recruits MCM helicases.
- In sum, CDC6 functions to have the Pre-RC poised to replicate DNA.
-Meanwhile, S-CYCLIN transcription is activated in late G1, and S-CYCLIN-CDK complex forms activating S-CDK that then phosphorylates PRE-RC and assemble the DNA POL + other machinery at the origin, while also activating HELICASES.
- S-CDK also prevents re-replication because it phosphorylates CDC6 for degradation once the ORC has fired for replication.
- S-CDK also phosphorylates MCMs and causes their export from nucleus.
Additional controls that prevent re-replication:
-_____ activity remains high during ___ and ___ causing ____ protein to always be phosphorylated and therefore preventing re-replication.
-_____ (different CDK) phosphorylates ____ and ____ proteins.
How does cell cycle control system reset itself to allow replication in the next cycle? At the end of mitosis, all _____ activity is reduced to 0, which results in _____ of ___ and ___, which allows for ____ assembly to occur again.
Additional controls that prevent re-replication:
-S-CDK activity remains high during G2 and MITOSIS causing CDC6 protein to always be phosphorylated and therefore preventing re-replication.
-M-CDK (different CDK) phosphorylates MCM and CDC6 proteins.
How does cell cycle control system reset itself to allow replication in the next cycle? At the end of mitosis, all CDK activity is reduced to 0, which results in DEPHOSPHORYLATION of CDC6 and MCM, which allows for PRE-RC assembly to occur again.
Activation of M Cyclin and triggering entry into mitosis:
-M cyclin [] gradually _____ during ___ and __ phases due to ____ of the gene.
-M cyclin needs to be properly ____ in order to be fully active.
- ____ will _____ M-CDK to begin activation
- ____ will _____ M-CDK in order to deactivate M-CDK
- ____ will remove inhibitory _____ in order to activate M-CDK
Activation of M Cyclin and triggering entry into mitosis:
-M cyclin [] gradually INCREASES during G2 and M phases due to TRANSCRIPTION of the gene.
-M cyclin needs to be properly PHOSPHORYLATED in order to be fully active.
- CAK will PHOSPHORYLATE M-CDK to begin activation
- WEE-1 will PHOSPHORYLATE M-CDK in order to deactivate M-CDK
- CDC25 will remove inhibitory PHOSPHATE in order to activate M-CDK
M-CDK phosphorylates proteins that are responsible for _____, ___ ____, and ____ ___ ______ _______
M-CDK phosphorylates proteins that are responsible for ASSEMBLY OF SPINDLE, CHROMOSOME CONDENSATION, and BREAKDOWN OF NUCLEAR ENVELOPE
Feedback Loops That Cause Increased M-CDK Activity:
- M-CDK inhibits ____ causing more active M-CDK to form
- M-CDK phosphorylates more ____, activating more of the _____ which leads to more activated M-CDK. This is a ____ feedback mechanism.
End result: as the cycle goes on, you no longer see ________ on new M-CDK.
Feedback Loops That Cause Increased M-CDK Activity:
- M-CDK inhibits WEE-1 causing more active M-CDK to form
- M-CDK phosphorylates more CDC25, activating more of the PHOSPHATASE which leads to more activated M-CDK. This is a POSITIVE feedback mechanism.
End result: as the cycle goes on, you no longer see INHIBITORY PHOSPHATE on new M-CDK.
Inactivation of M-CDK occurs primarily though ___ ____ via _____.
M-CDK activates ______ during _______.
Inactivation of M-CDK occurs primarily though PROTEIN DEGRADATION via UBIQUITINATION.
M-CDK activates UB-DEGRADATION SYSTEM during END OF M PHASE.
G1 phase is characterized by ___________.
Mechanisms to ensure this:
- ______-mediated _____ of Cdks
- _____ accumulation
- Decreased _____ transcription, which is mediated by ___ protein and _____ TF.
G1 phase is characterized by ABSENCE OF CDK ACTIVITY.
Mechanisms to ensure this:
- UB-mediated DEGRADATION of Cdks
- CYCLIN KINASE INHIBITOR (CKI) accumulation
- Decreased CYCLIN transcription, which is mediated by RB protein and E2F TF.
How do CKIs work?
-They function by ______ the CDK
How do CKIs work?
-They function by BINDING the CDK
Decreased cyclin transcription- Rb Protein:
-_____ protein is a TF that regulates expression of many genes required for entry into __ phase including ____ and __ cyclins.
- __ function is controlled by Rb. During __, Rb binds the TF and blocks it’s activity. This results in the above downstream genes not being transcribed.
- When cells receive _______ to divide, _____ accumulates and _____ Rb, which ____ the affinity of Rb to ___ which results in expression of ___ and ___ _____.
Decreased cyclin transcription- Rb Protein:
-E2F protein is a TF that regulates expression of many genes required for entry into S phase including G1/S and S cyclins.
- E2F function is controlled by Rb. During G1, Rb binds the TF and blocks it’s activity. This results in the above downstream genes not being transcribed.
- When cells receive EXTRACELLULAR SIGNAL to divide, G1-CDK accumulates and PHOSPHORYLATES Rb, which DECREASES the affinity of Rb to E2F which results in expression of G1/S and S CYCLINS.
Rb Feedback Loops:
-Once ____ is released by Rb inactivation, ____ then increases it’s own expression via binding it’s own promoter.
- ____ expression leads to production of ___ ____ and ____ which in turn phosphorylates more Rb and releases more ____.
- The increase in _____ and ____ activities enhances phosphorylation of _______ and ____, leading to their destruction in the proteasome, and as a consequence, activate more ____ and ____.
Rb Feedback Loops:
-Once E2F is released by Rb inactivation, E2F then increases it’s own expression via binding it’s own promoter.
- E2F expression leads to production of G1/S CDKS and S CDKS which in turn phosphorylates more Rb and releases more E2F.
- The increase in G1/S CDKS and S CDK activities enhances phosphorylation of UB LIGASES and CKI, leading to their destruction in the proteasome, and as a consequence, activate more G1/S CDK and S CDK.
G2 DNA Checkpoint
-When DNA is damaged in late G2 before mitosis, the DNA sends a signal via _____ that blocks ____ activity.
-Thus, without ____, M-CDK remains _____ and remains inactive.
G2 DNA Checkpoint
-When DNA is damaged in late G2 before mitosis, the DNA sends a signal via DOUBLE STRANDED BREAKS that blocks CDC25 activity.
-Thus, without CDC25, M-CDK remains PHOSPHORYLATED and remains inactive.
