During these processes meiotic recombination plays a critica

During these processes, meiotic recombination plays a critical role by physically associating homologs and ensures accurate chromosome segregation. In addition, meiotic recombination redistributes genetic material between homologs, resulting in haplotype diversity among progeny, impacting ecological adaptability and species evolution. Meiotic recombination is initiated by the enzymatically mediated formation of double strand break (DSB), followed by strand invasion, DNA synthesis and ligation. Despite the fact that DNA synthesis is an essential step in these pathways, relatively little is known about the proteins that facilitate or regulate it. Recently, a number of reviews have summarized the advances of other meiotic processes 3., 4., 5., 6., 7., 8., 9.. In this review, we will briefly discuss pre-meiotic DNA replication, followed by a more extensive review of the DNA synthesis gene products and their cofactors that are important for meiotic recombination. We will emphasize the results from recent molecular and genetic studies of DNA synthesis related genes in Arabidopsis, but also draw on data from other organisms as appropriate. Using these data, we propose a new model of type I meiotic recombination and provide new insights into the role of DNA synthesis in differentiating meiotic recombination pathways.
Pre-meiotic DNA replication Much of our understanding of pre-meiotic replication comes from studies using Saccharomyces cerevisiae. Initiation of both pre-meiotic and pre-mitotic DNA replication are similar in that they both require the MiniChromosome Maintenance (MCM) proteins for pre-replicative complex installation 10., 11., as well as leading strand and lagging strand replicative DNA polymerases and their associated factors. In S. cerevisiae, Cell Division Cycle 45 (CDC45), together with the MCM complex, is required for mitotic DNA replication initiation 12., 13.. The Xenopus CDC45 homologue has been demonstrated to load DNA polymerase α onto DNA [14]. The Arabidopsis CDC45 homologue is highly expressed in young flower buds [15], suggesting a role in meiosis. Arabidopsis CDC45 null ro bio 2 have an embryonic lethal phenotype, but RNAi knock-down transgenic plants (AtCDC45) enable the observation of adult phenotypes and the demonstration that a decrease in AtCDC45 transcripts results in reduced fertility. Chromosome spreads from AtCDC45 meiocytes revealed fragmented chromosomes, which are independent of SPO11-catalyzed meiotic DSBs. This result suggests that the chromosome fragments in AtCDC45 meiocytes are likely caused by incomplete pre-meiotic DNA replication. Interestingly, in mouse, the Cyclin Dependent Kinase CDK2, which recruits CDC45 to the replication fork, is indispensable for chromosome segregation in meiosis but not for mitotic cell division [16]. Several other differences between mitotic DNA replication and pre-meiotic DNA replication have been reported. The temperature-sensitive pat1 mutant from Schizosaccharomyces pombe grows normally at permissive temperatures, but at 36 °C, haploid cell can undergo DNA replication and two rounds of meiotic nuclear division to generate four uneven nuclear bodies, resulting in cell death [17]. In the pat1 mutant background, at permissive temperatures, a mutation of the catalytic subunit of DNA polymerase δ, CDC6/Cdc18, does not affect DNA replication during S phase, but causes a failure of the cell to enter M phase, reflecting checkpoint surveillance during mitotic S-M phase transition. By contrast, at the restrictive temperature, the pat1 cdc6/cdc18 double mutant is able to complete both pre-meiotic DNA replication and the subsequent meiotic progression [18], indicating a difference in checkpoint control between pre-meiotic and mitotic S phase. Another difference is the prolonged S phase of pre-meiotic DNA replication [19]. A recent study in S.cerevisiae provides evidence that the initiation sites of meiotic recombination by the programmed DSB formation is coordinated with the pre-meiotic DNA replication [20]. The mechanism for linking replication with DSB formation was revealed by the discovery of the cyclin dependent kinase DDK and its recruitment to the replication fork by two replisome components; furthermore, DDK-dependent phosphorylation of Mer2 is required for subsequent DSB formation [20].