11 Control of S Phase

Abstract

Sustained cell proliferation requires the duplication and segregation between daughter cells of every cell constituent. Because chromosomes are present in only one or two copies per cell, their duplication and segregation are particularly tightly regulated. To ensure that daughter cells inherit at least one copy of each of their genes and to maintain an appropriate balance in their relative numbers, the vast majority of eukaryotic cells replicate each sequence in their genomes once and only once per cell cycle. To ensure that daughter cells inherit sufficient but not excessive cytoplasm for the execution of their genetic programs, i.e., for protein synthesis, the duplication and segregation of chromosomes must occur no more or less frequently than cells duplicate the rest of their constituents. Finally, to ensure that cells maintain their ploidy, which is essential if they are to contribute to the germ line, reduplication must not recur until sister chromatids have been segregated at anaphase. STARTING DNA REPLICATION IN G 1 Coordinating DNA Replication and Cell Growth Pulse labeling with radioactive tracers showed that DNA replication occupies a defined window within the interdivision period, which is separated from the previous and preceding M phases by two gap periods, called G 1 and G 2 , respectively (Howard and Pelc 1951). Chromosome duplication and segregation are therefore periodic processes. Unlike chromosomes, most cellular constituents like ribosomes and enzymes are present in large numbers and are synthesized fairly continuously during the cell cycle (Mitchison 1970). During sustained cell proliferation, successive rounds of DNA replication and chromosome segregation...