Restriction point
The restriction point (R) is a point in G1 of the animal cell cycle at which the cell becomes "committed" to the cell cycle and after which extracellular proliferation stimulants are no longer required.
Originally, Temin showed that chicken cells reach a point at which they are committed to replicate their DNA and are not dependent on extracellular signals. About 20 years later, in 1973, Arthur Pardee demonstrated that a single restriction point exists in G1. Previously, G1 had been defined simply as the time between mitosis and S phase. No molecular or morphological place-markers for a cell's position in G1 were known. Pardee used a double-block method in which he shifted cells from one cell cycle block (such as critical amino acid withdrawal or serum withdrawal) to another and compared each block's efficiency at preventing progression to S phase. He found that both blocks in all cases examined were equally efficient at blocking S phase progression, indicating that they must all act at the same point in G1, which he termed the "restriction point", or R-point.
In 1985, Zetterberg and Larsson discovered that, in all stages of the cell cycle, serum deprivation results in inhibition of protein synthesis. Only in postmitotic cells (i.e. cells in early G1) did serum withdrawal force cells into quiescence (G0). In fact, Zetterberg found that virtually all of the variability in cell cycle length can be accounted for in the time it takes the cell to move from the restriction point to S phase.
Except for early embryonic development, most cells in multicellular organisms persist in a quiescent state known as G0, where proliferation does not occur, and cells are typically terminally differentiated; other specialized cells continue to divide into adulthood. For both of these groups of cells, a decision has been made to either exit the cell cycle and become quiescent (G0), or to reenter G1.
A cell's decision to enter, or reenter, the cell cycle is made before S-phase in G1 at what is known as the restriction point, and is determined by the combination of promotional and inhibitory extracellular signals that are received and processed. Before the R-point, a cell requires these extracellular stimulants to begin progressing through the first three sub-phases of G1 (competence, entry G1a, progression G1b). After the R-point has been passed in G1b, however, extracellular signals are no longer required, and the cell is irreversibly committed to preparing for DNA duplication. Further progression is regulated by intracellular mechanisms. Removal of stimulants before the cell reaches the R-point may result in the cell's reversion to quiescence. Under these conditions, cells are actually set back in the cell cycle, and will require additional time (about 8 hours more than the withdrawal time in culture) after passing the restriction point to enter S phase.
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