mitotic DNA replication checkpoint signaling

Definition

Target type: biologicalprocess

A signal transduction process that contributes to a mitotic DNA replication checkpoint. [GOC:mtg_cell_cycle]

Mitotic DNA replication checkpoint signaling is a critical cellular mechanism that ensures accurate and complete DNA replication before cells enter mitosis. This checkpoint is essential for preventing genomic instability and maintaining the integrity of the genome. The process involves a complex interplay of proteins, sensors, transducers, and effectors that monitor DNA replication progress and activate signaling pathways to arrest the cell cycle in response to replication stress.

The checkpoint system is activated by a variety of DNA replication stresses, such as stalled replication forks, double-strand breaks, and nucleotide depletion. These stresses trigger the activation of checkpoint sensors, which are specialized proteins that bind to damaged or stalled DNA replication machinery. Some of the key sensors involved in this process include ATR (Ataxia telangiectasia mutated and Rad3-related), ATM (Ataxia Telangiectasia Mutated), and CHK1 (checkpoint kinase 1).

Once activated, the sensors recruit and activate downstream signaling molecules, including transducers and effectors. Transducers like ATRIP and RAD9, act as mediators, relaying the signal from the sensors to the effector kinases. Effector kinases, such as CHK1 and CHK2 (checkpoint kinase 2), phosphorylate downstream targets, ultimately leading to cell cycle arrest.

The primary target of CHK1 is the CDC25A phosphatase, which is responsible for activating cyclin-dependent kinases (CDKs), the key regulators of cell cycle progression. By inhibiting CDC25A, CHK1 prevents the activation of CDKs and thus arrests the cell cycle in G2 phase, preventing entry into mitosis.

CHK1 activation also leads to the stabilization of p53, a tumor suppressor protein that promotes cell cycle arrest and apoptosis. This further reinforces the cell cycle checkpoint and prevents the propagation of damaged or incompletely replicated DNA.

Furthermore, CHK1 can influence DNA repair mechanisms by promoting the recruitment of DNA repair factors to sites of damage, facilitating the repair of damaged DNA before cell division.

In summary, mitotic DNA replication checkpoint signaling is a complex and tightly regulated process that ensures the faithful duplication of the genome and prevents the propagation of genomic instability. The checkpoint system is essential for maintaining cellular integrity and preventing the development of cancer and other genetic diseases.'
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Proteins (1)

Compounds (3)