Surveillance Mechanisms in Cell Cycle Regulation
Surveillance mechanisms known as checkpoint pathways establish dependencies among cell cycle events and ensure that the next cell cycle event does not occur prior to the completion of a preceding event.
Checkpoint pathways consist of sensors that monitor a particular cellular event, a signaling pathway, and an effector that halts cell cycle progression and activates repair pathways when necessary.
Growth and cell division are integrated during G1 in most organisms. Reduced macromolecule biosynthesis delays cell cycle entry.
Cells are able to detect and respond to a wide variety of DNA damage, and their response differs depending on the cell cycle stage that cells are in.
In response to DNA damage, two related protein kinases, ATM and ATR, are recruited to the site of the damage, where they activate signaling pathways that lead to cell cycle arrest, repair, and under some circumstances, apoptosis.
The spindle assembly checkpoint pathway, which prevents premature initiation of anaphase, utilizes Mad2 and other proteins to regulate APC/CCdc20, which targets securin and mitotic cyclins for ubiquitinylation.
The spindle position checkpoint pathway prevents mitotic CDK inactivation when the spindle is mispositioned. In this pathway, localized activators and inhibitors and a sensor that shuttles between them allow cells to sense spindle position.
The Hippo family of signal transduction pathways has been repurposed during evolution. Its function in coordinating exit from mitosis and cytokinesis with chromosome segregation in fungi has been replaced with coordination of tissue growth with tissue organization in metazoans.