Cell cycle checkpoint

Cell cycle checkpoints are control mechanisms in eukaryotic cells which ensure proper division of the cell. They play a critical role in maintaining the stability of the cell's genome by preventing the cell cycle from proceeding until certain conditions are met. These checkpoints are crucial for correcting errors, such as DNA damage or incomplete DNA replication, thus preventing the propagation of damaged or incomplete genetic material to daughter cells.

Overview

The cell cycle is divided into distinct phases: G1, S phase (DNA synthesis), G2, and M phase (mitosis). Cell cycle checkpoints occur at key points between these phases, acting as sensors to determine if the cell is in the proper condition to divide. The main checkpoints are the G1 checkpoint, the G2/M checkpoint, and the metaphase (M) checkpoint.

G1 Checkpoint

The G1 checkpoint, also known as the "restriction point," is located at the end of the G1 phase. It assesses whether the cell is large enough, has sufficient nutrients, and has undamaged DNA before it commits to DNA replication. If conditions are not favorable, the cell can enter a resting state known as G0.

S Phase Checkpoint

During the S phase, the cell replicates its DNA. The S phase checkpoint ensures that DNA replication is complete and accurate. It also detects any DNA damage and halts progression until the damage is repaired.

G2/M Checkpoint

The G2/M checkpoint occurs at the end of the G2 phase, just before mitosis. This checkpoint verifies that all DNA has been replicated and that any DNA damages have been repaired. It also ensures that the cell has reached adequate size to undergo mitosis.

Metaphase (M) Checkpoint

The metaphase checkpoint, also known as the spindle assembly checkpoint, occurs during mitosis. It ensures that all the chromosomes are properly attached to the mitotic spindle before the cell divides. This prevents the unequal distribution of chromosomes, known as aneuploidy, to the daughter cells.

Regulation

Cell cycle checkpoints are regulated by a complex network of signaling pathways involving cyclins, cyclin-dependent kinases (CDKs), and various checkpoint proteins such as p53, ATM, and ATR. These proteins work together to detect problems and halt the cell cycle progression until the issues are resolved.

Clinical Significance

Defects in cell cycle checkpoints can lead to uncontrolled cell division and are a hallmark of cancer. Understanding the mechanisms of cell cycle control has been crucial in developing chemotherapy and radiation therapy treatments, which often target rapidly dividing cells by exploiting the vulnerabilities in their checkpoint controls.

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  Cell cycle with cyclins and checkpoints

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  Cyclin B-Cdk1 hysteresis graph

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  MAPK cascade

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  Spindle chromosomes