Meta-Biol

• Pathways

The activity of the APC/C must be appropriately regulated during the cell cycle to ensure the timely degradation of its substrates. Of particular importance is the conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase. Phosphorylation of both the APC/C complex and Cdh1 regulate this conversion. During mitosis, several APC/C subunits are phosphorylated increasing the activity of APC/C:Cdc20. However, phosphorylation of Cdh1 by mitotic Cyclin:Cdk complexes prevents it from activating the APC/C. Dephosphorylation of Cdh1 in late anaphase by Cdc14a results in the activation of APC/C:Cdh1 (reviewed in Castro et al, 2005).

The events of replication of the genome and the subsequent segregation of chromosomes into daughter cells make up the cell cycle. DNA replication is carried out during a discrete temporal period known as the S (synthesis)-phase, and chromosome segregation occurs during a massive reorganization of cellular architecture at mitosis. Two gap-phases separate these cell cycle events: G1 between mitosis and S-phase, and G2 between S-phase and mitosis. Cells can exit the cell cycle for a period and enter a quiescent state known as G0, or terminally differentiate into cells that will not divide again, but undergo morphological development to carry out the wide variety of specialized functions of individual tissues.

A family of protein serine/threonine kinases known as the cyclin-dependent kinases (CDKs) controls progression through the cell cycle. As the name suggests, the kinase activity of the catalytic subunits is dependent on binding to cyclin partners, and control of cyclin abundance is one of several mechanisms by which CDK activity is regulated throughout the cell cycle.

A complex network of regulatory processes determines whether a quiescent cell (in G0 or early G1) will leave this state and initiate the processes to replicate its chromosomal DNA and divide. This regulation, during the Mitotic G1-G1/S phases of the cell cycle, centers on transcriptional regulation by the DREAM complex, with major roles for D and E type cyclin proteins.

Chromosomal DNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of each chromosome are formed. A key aspect of the regulation of DNA replication is the assembly and modification of a pre-replication complex assembled on ORC proteins.

Mitotic G2-G2/M phases encompass the interval between the completion of DNA synthesis and the beginning of mitosis. During G2, the cytoplasmic content of the cell increases. At G2/M transition, duplicated centrosomes mature and separate and CDK1:cyclin B complexes become active, setting the stage for spindle assembly and chromosome condensation at the start of mitotic M phase. Mitosis, or M phase, results in the generation of two daughter cells each with a complete diploid set of chromosomes. Events of the M/G1 transition, progression out of mitosis and division of the cell into two daughters (cytokinesis) are regulated by the Anaphase Promoting Complex.

The Anaphase Promoting Complex or Cyclosome (APC/C) plays additional roles in regulation of the mitotic cell cycle, insuring the appropriate length of the G1 phase. The APC/C itself is regulated by phosphorylation and interactions with checkpoint proteins.

The replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried out during a discrete temporal period known as the S (synthesis)-phase, and chromosome segregation occurs during a massive reorganization to cellular architecture at mitosis. Two gap-phases separate these major cell cycle events: G1 between mitosis and S-phase, and G2 between S-phase and mitosis. In the development of the human body, cells can exit the cell cycle for a period and enter a quiescent state known as G0, or terminally differentiate into cells that will not divide again, but undergo morphological development to carry out the wide variety of specialized functions of individual tissues.

A family of protein serine/threonine kinases known as the cyclin-dependent kinases (CDKs) controls progression through the cell cycle. As the name suggests, the activity of the catalytic subunit is dependent on binding to a cyclin partner. The human genome encodes several cyclins and several CDKs, with their names largely derived from the order in which they were identified. The oscillation of cyclin abundance is one important mechanism by which these enzymes phosphorylate key substrates to promote events at the relevant time and place. Additional post-translational modifications and interactions with regulatory proteins ensure that CDK activity is precisely regulated, frequently confined to a narrow window of activity.

In addition, genome integrity in the cell cycle is maintained by the action of a number of signal transduction pathways, known as cell cycle checkpoints, which monitor the accuracy and completeness of DNA replication during S phase and the orderly chromosomal condensation, pairing and partition into daughter cells during mitosis.

Replication of telomeric DNA at the ends of human chromosomes and packaging of their centromeres into chromatin are two aspects of chromosome maintenance that are integral parts of the cell cycle.

Meiosis is the specialized form of cell division that generates haploid gametes from diploid germ cells, associated with recombination (exchange of genetic material between chromosomal homologs).