DNA Replication in S. pombe

Abstract

One of the major feats accomplished by proliferating cells is the duplication of the genome once each cell cycle. In rapidly growing S. pombe cells this process occurs in a brief S phase early in the cell cycle, roughly coinciding with septum formation and cell separation. Each of the three chromosomes is replicated with remarkable fidelity to generate the two sister chromosomes that will be distributed to daughter cells at the subsequent mitosis. DNA synthesis is initiated at multiple internal sites along the chromosomal DNA and has to be highly regulated. (1) Initiation sites (origins) must be dispersed along the chromosomal DNA at frequent enough intervals to allow timely completion of genome duplication. (2) Initiation of DNA synthesis at the various chromosomal sites must be temporally coordinated to ensure that replication is completed before mitosis. (3) Initiation events must be confined to the original parental genome so that only two progeny genomes are produced during each cell cycle. The mechanisms that regulate DNA replication in S. pombe and other eukaryotes are only partially understood at this time. Based largely on studies in S. cerevisiae, S. pombe and Xenopus laevis, we have a general picture of the process, but the biochemical details are still largely obscure (Stillman 1996; Kelly and Brown 2000; Bell and Dutta 2002).