Meiotic DNA Replication

Abstract

Chromosome replication is a basic biological process that is essential for cellular proliferation. Owing to its fundamental nature the process of DNA replication is highly conserved among eukaryotic organisms. In the course of a typical somatic cell cycle, cells are “born” in G1 phase. Throughout this phase the cells grow in size increasing their mass and their protein synthetic capacity. As cells grow during G1 they monitor their size and protein synthetic capacity along with a variety of parameters in the external milieu including nutrient availability (Hartwell, 1974). When the internal and external environments are deemed to be suitable, the cell will commit to a cell division cycle. Initiating a cell cycle is a serious matter for yeast cells in that once they initiate the program they are committed to its completion (Hartwell, 1974). Should the cell have insufficient resources or capacity to successfully complete division the result is arrest and inevitable loss of viability. The decision to initiate a division cycle is taken at START in the budding yeast Saccharomyces cerevisiae; this event is referred to as R, the restriction point in mammalian cells (Hartwell, 1974; Pardee, 1974). If conditions are appropriate for proliferation, G1 phase cells will make the transition to S-phase where DNA replication ensues followed by progression through G2 and chromosome segregation at mitosis followed by completion of the cycle at cytokinesis. Prior to completing the START transition and committing to a round of cell division S. cerevisiae can adopt several alternative fates. Haploid cells can conjugate with a partner of the opposite mating type to form diploids (Cross et al., 1988). Alternatively, both haploid and diploid cells are capable of entering a quiescent state in response to deprivation of some nutrients (Gray et al., 2004). Under the appropriate conditions diploid MATa/ cells can exit the mitotic cell cycle and initiate the meiotic differentiation program leading to sporulation (Kupiec et al., 1997). This differentiation program is triggered by starvation for nitrogen and glucose. Upon encountering these conditions diploid S. cerevisiae will arrest in G1 phase with unreplicated DNA. The meiotic differentiation process initiates from G1 phase where the starved cells accumulate, and progresses through premeiotic DNA replication followed by extensive homologous recombination. Meiotic recombination is followed by two consecutive rounds of chromosome segregation, the meiosis I (reductional) division, and meiosis II (equational) division. Significantly, these two rounds of chromosome division occur without an intervening S-phase hence the meiotic progeny are haploid and the haploid nuclei are encapsulated in spores that are highly resistant to environmental insult. Hence, with regard to chromosome metabolism, the meiotic program resembles a somatic