Cyclin A

Protein family

Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. The stages that a cell passes through that culminate in its division and replication are collectively known as the cell cycle Since the successful division and replication of a cell is essential for its survival, the cell cycle is tightly regulated by several components to ensure the efficient and error free progression through the cell cycle. One such regulatory component is cyclin A which plays a role in the regulation of two different cell cycle stages.

Cyclin A was first identified in 1983 in sea urchin embryos. Since its initial discovery, homologues of cyclin A have been identified in numerous eukaryotes including Drosophila, Xenopus, mice, and in humans but has not been found in lower eukaryotes like yeast. The protein exists in both an embryonic form and somatic form. A single cyclin A gene has been identified in Drosophila while Xenopus, mice and humans contain two distinct types of cyclin A: A1, the embryonic specific form, and A2, the somatic form. Cyclin A1 is prevalently expressed during meiosis and early on in embryogenesis. Cyclin A2 is expressed in dividing somatic cells. which thereby activates the enzymatic activity of its CDK partner. Cyclin A is the only cyclin that regulates multiple steps of the cell cycle. Cyclin A has a second function in S phase. In addition to initiating DNA synthesis, Cyclin A ensures that DNA is replicated once per cell cycle by preventing the assembly of additional replication complexes. This is thought to occur through the phosphorylation of particular DNA replication machinery components, such as CDC6, by the cyclin A/CDK2 complex. Activated p53 turns on genes for p21. P21 is a CDK inhibitor that binds to several cyclin/CDK complexes, including cyclin A CDK2/1 and cyclin D/CDK4, and blocks the kinase activity of CDKs. Activated p21 can bind cyclin D/CDK4 and render it incapable of phosphorylating pRb. PRb remains hypophosphorylated and binds E2F. E2F is unable to activate the transcription of cyclins involved in cell cycle progression, such as cyclin A and the cell cycle is arrested at G1. Cell cycle arrest allows the cell to repair DNA damage before the cell divides and passes damaged DNA to daughter cells.