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Overview

Growth and the Cell Cycle
One of the most fundamental aspects of eukaryotic cell biology is the control of the cell division cycle. Such control is an essential aspect of the dramatic morphological changes that occur during animal development. During proliferation, progress through the cell cycle assures that cell division accompanies growth. In contrast, terminal differentiation is typically preceded by cell cycle arrest and the cessation of proliferation. Breakdowns in cell cycle control can have drastic consequences: mutation of certain genes that directly influence the activity of the cell cycle machinery can contribute to the deregulated growth typical of cancer. Thus, an understanding of the mechanisms of normal cell cycle control is critical for both our understanding of development and of oncogenesis.
The canonical eukaryotic cell division cycle is usually described as having four phases that occur in a precise order: G1-S-G2-M. A powerful paradigm for cell cycle control emerged in the last decade from studies in yeast, frog extract systems, and mammalian tissue culture cells. In this view, an oscillating molecular "engine" or "clock" ensures the ordered progression of events from one phase to the next, and "checkpoint controls" ensure that one phase is completed before the next is initiated. The central component of this molecular engine is a family of serine/threonine (S/T) protein kinases consisting of a catalytic subunit (cdk; cyclin dependent kinase) bound to a positive regulatory subunit from the cyclin family. Activation of different cyclin/cdk complexes stimulates progress through the major phase transitions of the cell cycle. Cdk activity is controlled at many levels, including cyclin/cdk complex formation, phosphorylation status, subcellular distribution, and association with inhibitory proteins (cki's).

Cell Cycle Control During Development...