Cell cycle events

II. PROTEIN KINASE ACTIVITY AND REGULATION OF CELL CYCLE EVENTS IN THE YEAST AND SELECTED VERTEBRATE MODEL SYSTEMS... 

Hartwell LH, Weinert TA 1989 Checkpoints controls that ensure the order of cell cycle events. Science 246 629-634... 

The different phases of the cell cycle include a number of highly ordered processes that ultimately lead to duphcation of the cell. The various cell cycle events are highly coordinated to occur in a defined order and with an exact timing, requiring precise control mechanisms. 

The ordered sequence of cell cycle events is ensured by different control loops that have an inhibitory or promoting effect on the progress(ion ) of the cell cycle. These are monitoring mechanisms that register the completion of important cell cycle events (e.g., complete DNA synthesis) and allow the transition to the next event (e.g., entry into mitosis) to occur. 

Many of the control mechanisms of the cell cycle are of intrinsic nature and are constitutive, i.e., they are operational in every cell cycle and ensure the ordering of the individual steps. However, other control mechanisms exist that are not active in every cell cycle these are only induced when defects are detected in central cell cycle events. These control mechanisms are known as checkpoints. An example of a checkpoint that is only activated when required is the DNA damage checkpoint (see 13.7). This is a biochemical pathway that detects DNA damage and creates a signal that arrests cells in the Gl, S or G2 phase of the cell cycle. 

Critical Cell Cycle Events and Cell Cycle Transitions... 

Herrup, K, Neve, R., Ackerman, S.L., Copani, A. (2004). Divide and die cell cycle events as triggers of nerve cell death. JNeurosci, 24, 9232-9. 

Hyaluronan is most prominent in the upper spinous and granular layers of the epidermis, where most of it is extracellular. The basal layer has HA, but it is predominantly intracellular, and is not easily leeched out during aqueous fixation. Presumably, basal keratinocyte HA is involved in cell cycling events, while the secreted HA in the upper outer layers of the epidermis are mechanisms for disassociation and eventual sloughing of cells. 

All eukaryotic cells have checkpoint regulation.32 A deletion in a gene encoding a checkpoint regulator abolishes the strict follow-up of one cell-cycle event after the other. Kim Nasmyth,33 therefore wants the term checkpoint to be applied only to those controls that ensure the ordered sequence of cell-cycle events. Following his definition, checkpoints are in essence inhibitory signalling pathways that keep a cell-cycle transition in check until the preceding operation is completed. 

The ordered sequence of cell cycle events is ensured by different control loops that have an inhibitory or promoting effect on the progress of the cell cycle. These are... 

Amphibian and invertebrate eggs and early embryos from synchronously fertilized eggs provide sources of extracts for biochemical studies of cell-cycle events. 

To test the functions of cyclin B In these cell-cycle events, all mRNAs in the egg extract were degraded by digestion with a low concentration of RNase, which then was Inactivated by addition of a specific inhibitor. This treatment destroys mRNAs without affecting the tRNAs and rRNAs required for protein synthesis, since their degradation requires much higher concentrations of RNase. When sperm nuclei were added to the RNase-treated extracts, the In nuclei replicated their DNA, but the increase in MPF activity and the early mitotic events (chromosome condensation and nuclear envelope disassembly), which the untreated extract supports, did not occur (Figure... 

To minimize the occurrence of such mistakes in cell-cycle events, a cell s progress through the cycle is monitored at several checkpoints (Figure 21-32). Control mechanisms that operate at these checkpoints ensure that chromosomes are intact and that each stage of the cell cycle is completed before the following stage is initiated. Our understanding of these control mechanisms at the molecular level has advanced considerably in recent years. 

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