Retta - L11

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Questions and Answers

What role do ATM and ATR proteins play in response to DNA damage during the cell cycle?

They promote apoptosis regardless of the damage level.

They activate proteins that inhibit cell cycle progression and initiate repair mechanisms. (correct)

They directly repair the DNA without influencing other proteins.

They only function during the M phase of the cell cycle.

Which protein can inhibit cell cycle progression by targeting p53?

Cdc25

Wee1 (correct)

p21

Cyclin

What is the consequence of excessive DNA damage that cannot be repaired effectively?

Permanent activation of cyclin-dependent kinases.

Cell cycle arrest without any further consequences.

Apoptosis to eliminate damaged cells. (correct)

Increased proliferation of abnormal cells.

How do Reactive Oxygen Species (ROS) contribute to DNA damage?

They can cause DNA oxidation leading to various types of DNA damage. Signup and view all the answers

What primary function do cyclins serve in the activation of cyclin-dependent protein kinases (Cdks)?

They bind with Cdks to bring about their enzymatic activity. Signup and view all the answers

In what situation can the repair mechanisms lead to abnormal cell survival?

When cells have accumulated mutations promoting abnormal proliferation. Signup and view all the answers

What occurs when a Cdk complex is fully activated?

It phosphorylates target proteins required for specific cell cycle transitions. Signup and view all the answers

What is the expected fate of most cells exposed to excessive DNA damage due to radiotherapy?

Most cells will die, but some may survive and proliferate. Signup and view all the answers

What triggers the phosphorylation of the Cdk to complete its activation?

Phosphorylation by Cdk-activating kinase (CAK). Signup and view all the answers

Which type of cyclin is crucial for initiating DNA replication?

S-cyclin Signup and view all the answers

Which cyclin primarily initiates the transition from G1 phase to S phase?

G1/S cyclin Signup and view all the answers

What regulatory mechanism prevents cyclin-Cdk complexes from being active in a cell cycle checkpoint?

Inhibitory phosphorylation by Wee1 Signup and view all the answers

During which phase is S cyclin up-regulated to activate DNA replication machinery?

S phase Signup and view all the answers

What role does the APC/C complex play during the cell cycle?

Degrades cyclins to regulate transitions Signup and view all the answers

Which CKI is activated in response to DNA damage and affects G1/S-Cdk complexes?

p21 Signup and view all the answers

What is the primary consequence of ubiquitination of a cyclin?

Labeling cyclin for degradation Signup and view all the answers

Which of the following statements correctly differentiates G1 cyclin from G1/S cyclin?

G1 cyclin is active in the G1 phase only. Signup and view all the answers

What primarily regulates the activity of the G1-Cdk complex during the cell cycle?

External growth factors and nutrients Signup and view all the answers

What triggers the downregulation of cyclin levels during the cell cycle?

Proteolysis and degradation Signup and view all the answers

How does Cdc25 phosphatase function within the cyclin-Cdk regulatory cycle?

It removes inhibitory phosphates from Cdk. Signup and view all the answers

What is the primary function of cell cycle checkpoints?

To regulate the transition between different phases of the cell cycle Signup and view all the answers

What occurs if the DNA is not fully replicated during the cell cycle?

A stop is enforced on the cell cycle until replication is complete Signup and view all the answers

How do checkpoints manage to halt the cell cycle?

Through negative intracellular signals that inhibit progression Signup and view all the answers

What is the consequence of a mutation in genes encoding proteins involved in checkpoints?

Promotion of cancer through abnormal proliferation Signup and view all the answers

What is the role of unattached chromosomes in the cell cycle?

They send negative signals that inhibit cell cycle progression Signup and view all the answers

Which checkpoint specifically monitors the attachment of chromosomes to the mitotic spindle?

M checkpoint Signup and view all the answers

What kind of signals do checkpoints primarily utilize to regulate the cell cycle?

Negative intracellular signals Signup and view all the answers

What happens during cell cycle breaks?

The cell pauses until issues are resolved, like DNA damage Signup and view all the answers

Which of the following describes the mechanism of checkpoints during the cell cycle?

They induce a halt until favorable conditions are met Signup and view all the answers

What initiates the halt in the cell cycle when a chromosome is not attached to the spindle?

A negative signal from the unattached chromosome Signup and view all the answers

Study Notes

Cell Cycle Checkpoints

Checkpoints regulate transitions between cell cycle phases by assessing internal and external factors.
Major checkpoints ensure DNA integrity, chromosomal attachment, and overall cell cycle conditions.
If unfavorable conditions exist, checkpoints pause the cell cycle until issues like DNA damage are repaired.

Mechanisms of Checkpoints

Checkpoints use negative signals to halt the cell cycle until conditions are favorable, rather than removing positive signals.
Unattached chromosomes generate negative signals that prevent cell cycle progression until all chromosomes are correctly attached.
DNA replication must be complete for the cell cycle to progress; incomplete DNA results in a stop signal.

DNA Damage and Checkpoint Regulation

ATM and ATR proteins sense DNA damage like double-strand breaks and single-strand lesions during S or G2 phases.
Activated ATM/ATR initiates p53 activation, which can block cell cycle progression or induce apoptosis if damage is irreparable.
External factors like radiation can cause mutations affecting checkpoint functionality, potentially leading to cancer development.

Reactive Oxygen Species (ROS) and DNA Damage

ROS, both endogenous and environmental, can induce DNA damage through oxidation.
Excessive DNA damage may trigger apoptosis or allow for abnormal cell survival, leading to potential cancerous growth.

Radiotherapy as a Cancer Treatment

Radiotherapy induces extensive DNA damage to trigger apoptosis in cancer cells.
Some cells repair and survive DNA damage, facilitating cancer progression despite treatment efforts.

Cyclin-Dependent Kinases (CDKs) Regulation

Cyclins activate CDKs by binding to them, initiating specific cell cycle processes.
CDK activity is temporally regulated, with cyclin concentrations varying throughout the cell cycle.
Cyclin-CDK complexes are critical for transitions between cell cycle phases, impacting key events like DNA replication and mitosis.

Cyclins and Their Functions

M-cyclin drives entry into M phase; S-cyclin triggers DNA replication initiation.
Cyclin concentrations peak just before their functional phase and degrade post-usage.

G1/S Cyclin and External Signals

G1 cyclin activates G1/S-Cdk, which promotes S phase entry upon sensing growth factors and nutrients.
APC/C checks chromosomal attachment during mitosis, ensuring cell cycle integrity.

CDK Inhibition Mechanisms

CDK complexes can be inhibited through additional phosphorylation by Wee1 kinase.
Cdc25 phosphatase reactivates CDK by removing inhibitory phosphate groups.

CDK Inhibitor Proteins (CKIs)

CKIs like p21, p16, and p27 inhibit CDK activity, providing additional regulatory control for cell cycle progression.
P53 activation leads to CKI expression, which prevents entry into the cell cycle when DNA damage occurs.

Role of Proteolysis in Cell Cycle Control

Ubiquitination targets cyclins for degradation via the proteasome to regulate their availability throughout the cell cycle.
This cyclical proteolysis mechanism ensures proper timing of cell cycle phase transitions and prevents uncontrolled proliferation.

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Description

This quiz explores the fundamental concepts of cell cycle checkpoints, including their role in regulating transitions between phases. It covers mechanisms of checkpoints, how they respond to DNA damage, and the involvement of specific proteins like ATM and ATR. Test your understanding of how these processes ensure cell integrity and proper function.