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Cell Cycle Checkpoints

Cell cycle checkpoints are critical for genomic stability, monitoring the progression of the cell cycle and initiating DNA repair. They play a key role in the DNA damage response, halting the cycle to fix lesions or trigger cell death to prevent mutations. These checkpoints are crucial in cancer prevention, as their dysfunction can lead to unregulated cell proliferation and oncogenesis. The p53 protein is a major regulator of these checkpoints, and its mutation is a common feature in many cancers. Techniques like FUCCI enable real-time visualization of cell cycle dynamics, aiding research into these vital processes.

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1

Position of cell cycle checkpoints

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Checkpoints located at key cell cycle phases to monitor progression and integrity.

2

Role of checkpoint proteins

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Evaluate cell's readiness for next phase, initiate DNA repair if needed.

3

Consequence of checkpoint failure

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Genetic errors transmitted, potential for disorders like cancer.

4

______ can be caused by both internal and external elements, and ______ play a key role in responding to this issue.

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DNA damage cell cycle checkpoints

5

Every day, a human cell experiences numerous ______, and the ______ halt the cell cycle for repair time.

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DNA lesions checkpoints

6

The prevention of mutation build-up and ______ is a critical function of the ______ in human cells.

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oncogenesis protective function

7

Function of G1/S checkpoint

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Assesses cell's resources for DNA synthesis; if adequate, initiates DNA replication.

8

Role of G2/M checkpoint

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Verifies DNA replication completeness and accuracy; ensures cell is ready for mitosis.

9

Purpose of spindle assembly checkpoint

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Confirms all chromosomes are correctly attached to spindle before allowing chromosome segregation.

10

The unchecked proliferation in cancer contributes to the accumulation of more mutations and ______ ______, which are characteristic signs of the disease.

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genomic instability

11

Differentiated cells that are not dividing enter a dormant phase called ______, where they are metabolically active but do not ______.

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G0 divide

12

During the G0 phase, differentiated cells do not engage cell cycle ______ because they no longer ______.

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checkpoints divide

13

Role of sperm signals in fertilization

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Sperm signals awaken egg from dormancy, prompting cell cycle re-entry, essential for embryogenesis.

14

Consequence of egg cell reactivation post-fertilization

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Egg reactivation leads to mitotic divisions, necessary for embryo development.

15

When DNA damage occurs, ______ can trigger cell cycle halt, DNA repair, or ______.

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p53 apoptosis

16

Frequent mutations in the ______ gene, responsible for p53, are associated with many ______ and checkpoint control failures.

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TP53 cancers

17

Studying ______ and other checkpoint regulators is vital for grasping and possibly disrupting ______ development.

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p53 cancer

18

Original FUCCI system fluorescent proteins

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Green and red fluorescent proteins used to visualize cell cycle phases.

19

FUCCI system advancements

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Incorporation of far-red and near-infrared proteins for enhanced imaging.

20

FUCCI's role in cell cycle checkpoints

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Enables study of checkpoint functions and regulation within the cell cycle.

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Understanding Cell Cycle Checkpoints

Cell cycle checkpoints are essential control mechanisms that ensure the correct progression of the cell cycle and the preservation of genomic stability. These checkpoints are strategically positioned at key points in the cell cycle to monitor and verify the successful completion of essential processes and to initiate DNA repair if necessary. A complex network of checkpoint proteins continuously evaluates whether the cell has met all the criteria to proceed from one phase to the next, thereby preventing the transmission of genetic errors that could lead to disorders, including cancer.
Fluorescent microscope slide shows dividing human cells with staining for cell structures in green, blue, pink and orange.

The Role of Checkpoints in DNA Damage Response

DNA damage can occur due to a variety of internal and external factors, and the cell cycle checkpoints are integral to the DNA damage response. The human cell is subject to numerous DNA lesions per day, and the checkpoints act to pause the cell cycle, allowing time for the repair mechanisms to correct the damage. If the damage is irreparable, checkpoints can trigger cell death to prevent the propagation of defective cells. This protective function is crucial in preventing the accumulation of mutations that could lead to oncogenesis.

Major Checkpoints in the Cell Cycle

The cell cycle contains several checkpoints, each with a specific function. The G1/S checkpoint, also known as the restriction point, evaluates if the cell has the necessary nutrients and energy to synthesize DNA. The G2/M checkpoint checks for complete and accurate DNA replication and prepares the cell for mitosis. The spindle assembly checkpoint, during mitosis, ensures that all chromosomes are properly attached to the spindle apparatus before chromosome segregation. These checkpoints are fundamental in maintaining the sequential and timely order of cell cycle events.

Checkpoint Dysfunction and Cancer

In cancer, mutations often impair the normal function of cell cycle checkpoints, allowing cells to proliferate without the usual regulatory constraints. This leads to the accumulation of further mutations and genomic instability, which are hallmarks of cancer. In contrast, non-proliferating, differentiated cells exit the cell cycle and enter a state of dormancy known as G0, where they remain metabolically active but no longer divide, and thus, cell cycle checkpoints are not engaged.

Checkpoint Regulation in Developmental Processes

The regulation of cell cycle checkpoints is vital not only for individual cell function but also for the development of multicellular organisms. For example, in sexual reproduction, the fertilization process involves the sperm delivering signals that awaken the egg cell from its dormant state, prompting it to re-enter the cell cycle. This reactivation is critical for the egg to undergo the mitotic divisions necessary for embryogenesis.

The p53 Tumor Suppressor and Checkpoint Control

The tumor suppressor protein p53 is a central component of the checkpoint control mechanisms at the G1/S and G2/M transitions. It orchestrates cellular responses to DNA damage and can induce cell cycle arrest, DNA repair, or apoptosis. Mutations in the TP53 gene, which encodes p53, are common in many cancers and can lead to a breakdown in checkpoint control. Research into p53 and other checkpoint regulators is essential for understanding and potentially intervening in cancer progression.

Visualizing Cell Cycle Dynamics with FUCCI

The Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) is a cutting-edge technique that allows for the visualization of cell cycle phases in living cells. This system employs fluorescent proteins that are selectively expressed and degraded during specific stages of the cell cycle, enabling real-time observation of cellular dynamics. The original FUCCI system utilized green and red fluorescent proteins, and newer versions have incorporated far-red and near-infrared proteins for improved imaging capabilities. Such tools are invaluable for researchers in dissecting the complex regulation of the cell cycle and the role of checkpoints.