nuclear fragmentation involved in apoptotic nuclear change

Definition

Target type: biologicalprocess

The breakdown of the nucleus into small membrane-bounded compartments, or blebs, each of which contain compacted DNA. [GOC:dph, GOC:mah, GOC:mtg_apoptosis, GOC:tb, ISBN:0721639976]

Nuclear fragmentation, a hallmark of apoptosis, is a complex and highly regulated process that dismantles the nucleus, ultimately leading to the demise of the cell. It involves a cascade of molecular events triggered by apoptotic signals, culminating in the breakdown of the nuclear envelope and the condensation and fragmentation of chromatin.

The process begins with the activation of caspases, a family of cysteine proteases. These enzymes are triggered by various apoptotic stimuli, including DNA damage, growth factor deprivation, and cytotoxic agents. Once activated, caspases cleave and activate downstream effector caspases, such as caspase-3, -6, and -7. These effector caspases play a critical role in nuclear fragmentation.

One of the key targets of caspase-3 is the nuclear lamins, a protein scaffold that provides structural support to the nuclear envelope. Cleavage of lamins by caspase-3 disrupts the integrity of the nuclear envelope, causing it to break down into smaller fragments. This fragmentation is accompanied by the condensation of chromatin, the DNA-containing material within the nucleus.

Caspases also cleave other nuclear proteins, including DNA repair enzymes and histone proteins. Cleavage of these proteins further contributes to the condensation and fragmentation of chromatin. The condensed chromatin fragments into smaller, dense masses called apoptotic bodies.

In addition to caspase-mediated cleavage, other factors contribute to nuclear fragmentation. These include:

- **DNA fragmentation:** Caspase-activated DNase (CAD), a nuclease activated by caspase-3, cleaves DNA at specific sites, generating DNA fragments of approximately 180 base pairs. This fragmentation is often used as a marker of apoptosis.

- **Mitochondrial involvement:** Mitochondria, the powerhouses of the cell, play a crucial role in apoptosis. They release cytochrome c, a protein that activates caspase-9, leading to the activation of the caspase cascade. Mitochondria also release other factors that contribute to nuclear fragmentation, such as AIF (apoptosis inducing factor).

- **Changes in nuclear membrane permeability:** During apoptosis, the nuclear envelope becomes permeable, allowing the entry of enzymes and other factors that contribute to nuclear fragmentation.

Nuclear fragmentation is a critical event in apoptosis, ensuring the controlled dismantling of the nucleus and the efficient removal of the apoptotic cell without triggering inflammation or damage to surrounding cells. This process is vital for maintaining tissue homeostasis and preventing the accumulation of damaged cells.'
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