L15 CDK mediated regulation of G1/S

What is the main role of cyclin

dependent kinases (CDKs) in the cell cycle?

How is cyclin expression regulated?

Cyclins are expressed in response to growth factors and transcriptional activation and degraded after completing their function

Why does cyclin degradation ensure forward progression of the cell cycle?

It prevents the same cell cycle stage from recurring, maintaining unidirectional progression

Name five positive regulatory mechanisms of CDKs.

1. Mitogen

2. Transcriptional regulation of cyclins

3. Cyclin binding

4. Activation by CDK activating kinase (CAK) phosphorylation

5. Removal of inhibitory phosphorylation

Name three negative regulatory mechanisms of CDKs.

1. CDK inhibitor proteins (CDKIs)

2. Inhibitory phosphorylation

3. Cyclin degradation via ubiquitin

proteasome system

How do mitogens influence cyclin expression?

Mitogens bind membrane receptors, activate MAPK signalling, and stimulate transcription factors like Myc to induce cyclin expression

Which transcription factor promotes cyclin D and E expression?

Myc

What is the major transcriptional regulator of S

phase genes?

Why are CDKs inactive without cyclin binding?

Cyclins induce conformational changes in the CDK T

How does CDK activating kinase (CAK) regulate CDK activity?

CAK phosphorylates the CDK at T160, increasing catalytic efficiency and activating the CDK

How do CDK inhibitor proteins (CDKIs) regulate S phase entry?

CDKIs bind cyclin

What must happen to CDKIs to allow S phase entry?

CDKIs must be degraded

How does sequential cyclin expression affect CDK activity?

It creates an increasing CDK activity profile that temporally regulates key cell cycle transitions

How does CDK activity prevent DNA from replicating more than once per cycle?

Low CDK activity allows replication licensing, intermediate CDK activity initiates replication, and high CDK activity prevents re

What is DNA replication licensing?

The process of loading replication factors (ORC, Cdc6, Cdt1, MCM2

Which protein complex recognizes replication origins?

Origin recognition complex (ORC)

Which factors interact with ORC to load MCM helicase complexes?

Cdc6 and Cdt1

When can DNA replication licensing occur?

Only during low CDK activity in early G1 phase

How does high CDK activity inhibit replication licensing?

Phosphorylates ORC, Cdc6, and Cdt1, weakening chromatin interactions and triggering proteasomal degradation of Cdt1

What is the role of MCM helicase in DNA replication?

MCM unwinds double

Which kinases activate MCM helicase?

CDKs and Dbf4

How is the replisome assembled?

DNA polymerases and accessory proteins are recruited to activated MCM helicases to complete replication machinery assembly

Why is CDK activity oscillation important for replication?

Low CDK activity allows licensing, intermediate CDK activity initiates replication, and high CDK activity prevents re

Which CDK

cyclin complex promotes S phase entry?

How does CDK activity ensure genetic stability?

By preventing re

What happens to replication licensing factors after replication initiation?

They are phosphorylated and degraded to prevent re

How does the Rb pathway connect to CDK regulation?

Cyclin D

What is the function of CDKIs like p27?

They bind cyclin

Which step marks pre

replication complex formation?

When are helicases activated at replication origins?

Late G1, as CDK activity rises and DDK phosphorylates MCM complexes

What is the function of the replisome?

The replisome is the multi

Why is DNA replication initiated bi

directionally?

How does oscillating CDK activity control the timing of replication?

It separates licensing, initiation, and prevents re

Which CDK

cyclin complex is active in G1/S?

Which CDK

cyclin complex is active in S phase?

Which kinases prevent re

licensing outside G1 phase?