Potential role of cyclin D₁in DNA damage response

Excerpt

In mammalian cells, cell cycle progression is governed by distinct cyclin-dependent kinases (cdks) whose activities are regulated by binding of their activating cyclin subunits and through negative regulation by inhibitor proteins such as p21. Cyclin levels oscillate in a phase-dependent manner, ensuring the stage-specific activation of cyclin/cdk complexes. The D-type cyclin levels are thought to act as sensors of the cellular environment: under conditions permissive for proliferation, D-type cyclins accumulate and facilitate the G₁ phase progression; whereas under restrictive conditions, D-type cyclin transcription is attenuated and the protein is destabilised via ubiquitin-mediated proteolysis. In addition to the normal cell cycle regulation, a member of D-type cyclins, cyclin D₁, has been implicated in the DNA damage response. Once activated, DNA damage responses disrupt the function of the cell cycle and can result in a number of outcomes including short-term or long-term cell cycle arrest, apoptosis and necrosis. Cyclin D₁ expression is often found deregulated in cancerous cells, particularly in those of the breast and the head/neck. …