Question

Describe briefly the cell cyle. Describe the  the role of cyclin-cdk complexes play in the cell cycle.  

Answer 1

Cell cycle:

• The cell cycle is the series of events which takes place in a cell that cause it to divide into two daughter cells.
• These events include the duplication of its DNA  or DNA replication and some of its organelles and subsequently following the partitioning of its cytoplasm and other components into two daughter cells by a process called  Cell division.
• The cell cycle is divided into two main stages - Interphase and the  Mitotic phase (M) (which includes  mitosis and cytokinesis).
• During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles.
• Interphase proceeds in three stages, G₁, S, and G₂.

• During mitotic phase, the sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These phases are sequentially known as: prophase, prometaphase, metaphase, anaphase, and telophase.

• Two key classes of regulatory molecules, cyclins and cyclin dependent kinases (CDKs), determines the cell's progress through the cell cycle.

• Cyclins form the regulatory subunits and CDKs are the catalytic subunits of an activated  heterodimer.
• Cyclins have no catalytic activity and CDKs are inactive in the absence of a partner cyclin. 
•  When activated by a bound cyclin, CDKs perform a common biochemical reaction called  Phosphorylation that activates or inactivates target proteins to orchestrate coordinated entry into the next phase of the cell cycle.

Role of cyclins and CDKs:

• Upon receiving a pro-mitotic extracellular signal, G₁  cyclin-CDK complexes become active to prepare the cell for S phase, promoting the expression of  transcription factors that in turn promote the expression of S cyclins and of enzymes required for  DNA replication.
•  The G₁ cyclin-CDK complexes also promote the degradation of molecules that function as S phase inhibitors.
• Mitotic cyclin-CDK complexes, which are synthesized but inactivated during S and G₂ phases, promote the initiation of mitosis by stimulating downstream proteins involved in chromosome condensation and  mitotic spindle assembly.
• A critical complex activated during this process is a ubiquitin ligase known as the  Anaphase Promoting Complex (APC), which promotes degradation of structural proteins associated with the chromosomal  kinetochore.
• APC also targets the mitotic cyclins for degradation, ensuring that telophase and cytokinesis can proceed.

 Action of cyclin-CDK complexes:

• Cyclin D is the first cyclin produced in the cells that enter the cell cycle.

• CDK4/6 and CDK2 are inactive because CDK4/6 are bound by  INK4 family members, limiting kinase activity.

• CDK2 complexes are inhibited by the CIP/KIP proteins such as p21 and p27.

•  When it is time for a cell to enter the cell cycle, which is triggered by a mitogenic stimuli, levels of cyclin D increase.

• In response to this trigger, cyclin D binds to existing CDK4/6, forming the active cyclin D-CDK4/6 complex.

• Cyclin D-CDK4/6 complexes in turn mono-phosphorylates the  retinoblastoma susceptibility protein (Rb) to pRb.

• The un-phosphorylated Rb tumour suppressor functions in inducing cell cycle exit and maintaining G0 arrest (senescence).

• All different mono-phosphorylated Rb isoforms inhibit E2F transcriptional program and are able to arrest cells in G1-phase.

• In general, the binding of pRb to E2F inhibits the E2F target gene expression of certain G1/S and S transition genes.

•  Cyclin E produced binds to  CDK2, forming the cyclin E-CDK2 complex, which pushes the cell from G₁ to S phase (G₁/S, which initiates the G₂/M transition).
•   Cyclin B-cdk1 complex activation causes breakdown of  nuclear envelope and initiation of  prophase, and subsequently, its deactivation causes the cell to exit mitosis.

 

Cell cycle

• The cell cycle is a series of steps where the chromosomes and other cell material double to make two copies.
• Then cell the divides into two daughter cells, each receiving one copy of the doubled material.
• The cell cycle is completed when each daughter cell is surrounded by its own outer membrane.
• The stages of the cell cycle include interphase, prophase, metaphase, anaphase, telophase.