IntroductionCells of sexually reproducing eukaryotes normally contain two equal (homologous) sets of chromosomes, one contributed by the father and the other by the mother during the fusion of gametes and the formation of a zygote. Meiosis is the cell division that reduces the number of chromosomes by half. It produces gametes or their precursor cells, each of which contains a haploid set consisting of randomly assorted parental chromosomes. These chromosomes are mosaics, because the original parental homologues have exchanged corresponding pieces by crossing-over. Thus, the function of meiosis is twofold -it compensates for the doubling of the chromosome number at fertilization and it provides the progeny with newly assorted sets of alleles, which is the basis of their genetic diversity.Crossing-over is initiated at multiple sites in recombining chromosomes by the enzymatic induction of double-strand breaks (DSBs). The resection of single strands at DSBs leads to the formation of gaps in the DNA. The missing bases are replenished by using the complementary sequence from the homologous chromosome as the template. This process is recombinogenic; that is, it can lead to the reciprocal exchange of DNA between the chromosomes involved (for review, see Keeney, 2001).In order to allow crossing-over, homologous parental chromosomes must pair during meiotic prophase via a ladderlike proteinaceous structure, the synaptonemal complex (SC) (for reviews, see Loidl, 1990;Zickler and Kleckner, 1999). The SC consists of two parallel axes (the lateral elements), to each of which the two chromatin threads of a single replicated chromosome are attached. The lateral elements are connected and kept at a distance of ~100 nm by the so-called transversal filaments. The ultrastructure of the SC is evolutionarily well conserved from protists to humans, although its molecular composition is far more heterogeneous.The fission yeast Schizosaccharomyces pombe features a meiosis that is unique in several respects. Most remarkably, it lacks an SC. Instead, so-called linear elements (LEs) appear during meiotic prophase (Olson et al., 1978;Bähler et al., 1993). LEs appear in the electron microscope (EM) as single lines of variable length, networks of interconnected lines or bundles of lines. These different morphological classes were found to prevail at different stages of meiotic prophase (Bähler et al., 1993), which suggests that their change in appearance is functionally related to chromosome pairing and/or recombination.Because a rec10 mutant lacks LEs, a structural or regulatory role of the Rec10 protein in LE formation has been proposed (Molnar et al., 2003). Apart from this indirect evidence, information on the molecular composition of LEs is scarce. Neither topoisomerase II nor Rec8 [which, in other organisms, constitute the cores along which lateral elements form (Klein et al., 1992;Klein et al., 1999)] delineate entire LEs (Hartsuiker et al., 1998;Parisi et al., 1999;Watanabe and Nurse, 1999), and S. pombe homologues of proteins prese...

DNA replication stress has been implicated in the etiology of genetic diseases, including cancers. It has been proposed that genomic sites that inhibit or slow DNA replication fork progression possess recombination hotspot activity and can form potential fragile sites. Here we used the fission yeast, Schizosaccharomyces pombe, to demonstrate that hotspot activity is not a universal feature of replication fork barriers (RFBs), and we propose that most sites within the genome that form RFBs do not have recombination hotspot activity under nonstressed conditions. We further demonstrate that Swi1, the TIMELESS homologue, differentially controls the recombination potential of RFBs, switching between being a suppressor and an activator of recombination in a sitespecific fashion.fission yeast ͉ genome stability ͉ TIMELESS

Translin is a conserved protein which associates with the breakpoint junctions of chromosomal translocations linked with the development of some human cancers. It binds to both DNA and RNA and has been implicated in mRNA metabolism and regulation of genome stability. It has a binding partner, translin-associated protein X (TRAX), levels of which are regulated by the translin protein in higher eukaryotes. In this study we find that this regulatory function is conserved in the lower eukaryotes, suggesting that translin and TRAX have important functions which provide a selective advantage to both unicellular and multi-cellular eukaryotes, indicating that this function may not be tissue-specific in nature. However, to date, the biological importance of translin and TRAX remains unclear. Here we systematically investigate proposals that suggest translin and TRAX play roles in controlling mitotic cell proliferation, DNA damage responses, genome stability, meiotic/mitotic recombination and stability of GT-rich repeat sequences. We find no evidence for translin and/or TRAX primary function in these pathways, indicating that the conserved biochemical function of translin is not implicated in primary pathways for regulating genome stability and/or segregation.

Most organisms form protein-rich, linear, ladder-like structures associated with chromosomes during early meiosis, the synaptonemal complex. In Schizosaccharomyces pombe, linear elements (LinEs) are thread-like, proteinacious chromosome-associated structures that form during early meiosis. LinEs are related to axial elements, the synaptonemal complex precursors of other organisms. Previous studies have led to the suggestion that axial structures are essential to mediate meiotic recombination. Rec10 protein is a major component of S. pombe LinEs and is required for their development. In this report we study recombination in a number of rec10 mutants, one of which (rec10-155) does not form LinEs, but is predicted to encode a truncated Rec10 protein. This mutant has levels of crossing over and gene conversion substantially higher than a rec10 null mutant (rec10-175) and forms cytologically detectable Rad51 foci indicative of meiotic recombination intermediates. These data demonstrate that while Rec10 is required for meiotic recombination, substantial meiotic recombination can occur in rec10 mutants that do not form LinEs, indicating that LinEs per se are not essential for all meiotic recombination.

Certain genomic loci, termed hot spots, are predisposed to undergo genetic recombination during meiosis at higher levels relative to the rest of the genome. The factors that specify hot-spot potential are not well understood. The M26 hot spot of Schizosaccharomyces pombe is dependent on certain trans activators and a specific nucleotide sequence, which can function as a hot spot in a position-and orientation-independent fashion within ade6. In this report we demonstrate that a linear element (LE) component, Rec10, has a function that is required for activation of some, but not all, M26-containing hot spots and from this we propose that, with respect to hot-spot activity, there are three classes of M26-containing sequences. We demonstrate that the localized sequence context in which the M26 heptamer is embedded is a major factor governing whether or not this Rec10 function is required for full hot-spot activation. Furthermore, we show that the rec10-144 mutant, which is defective in full activation of ade6-M26, but proficient for activation of other M26-containing hot spots, is also defective in the formation of LEs, suggesting an intimate link between higher-order chromatin structure and local influences on hot-spot activation.

Homologous chromosome pairing is a central feature of meiosis I, contributing to the correct segregation of chromosomes during meiosis. The fission yeast, Schizosaccharomyces pombe, has been widely used to study meiotic chromosome dynamics, partly because studies in this yeast are simplified due to the lack of postpairing synaptic structures. Chromosome pairing in Sz. pombe occurs differentially throughout the genome. Telomeres cluster at the spindle pole body (SPB) at the onset of meiosis, imposing a spatial restriction on pairing events. Subsequently, centromeres dissociate from the SPB and pair in a recombination-and heterochromatin (Swi6)-independent fashion. Pairing of telomere distal regions occurs during meiotic prophase, concomitant with a dynamic association/dissociation of homologous regions, with interhomologue associations becoming increasingly stable. The stabilization of paired regions is enhanced by factors required for the initiation of meiotic recombination, suggesting that recombination stabilizes paired regions. However, substantial pairing is initiated in the absence of recombination; this is dependent upon another factor, the conserved Meu13 protein, demonstrating that recombination is not required for initial pairing interactions. During meiotic prophase Sz. pombe exhibits a pronounced dynein-dependent nuclear oscillation, which drives the pairing of centromeric and interstitial regions. Dynein is also required for the significant levels of achiasmate reductional segregation observed in Sz. pombe, possibly implicating the centromere-associated pairing with achiasmate homologue segregation. Whilst Sz. pombe does not form discernable synaptic structures continuously along the meiotic chromosomes, it does form proteinacious, meiosis-specific, linear structures (linear elements). However, the role, if any, of these structures in mediating homologue pairing is unknown.

Aqueous extracts of Schistosoma mansoni eggs have been shown to have fibrinolytic activity inhibitable by a serine protease inhibitor. Fibrinolytic activity was not present in extracts of either adult worms or cercariae. A 27 kDa enzyme that was proteolytically active on fibrinogen in zymography and that degraded fibrinogen in a pattern similar to that of plasmin, is presumed to be responsible for the schistosome egg fibrinolytic activity. Anti-human fibrinogen antisera were shown to have antibodies that cross-reacted with mouse fibrinogen in Western immunoblots. Electroblotted sera from S. mansoni-infected and control uninfected mice displayed different antigenic profiles when probed with the cross-reactive anti-human fibrinogen antibodies, suggesting an alteration in mouse host fibrinogen metabolism as a result of the parasitic infection. We discuss the possibility that modulation of fibrinogen metabolism is a factor in a recently discovered anti-atherogenic effect exerted by schistosomes.

Meiotic recombination predominantly occurs at genomic loci referred to as recombination hotspots. The fission yeast, Schizosaccharomyces pombe, has proved to be an excellent model organism in which to study details of the molecular basis of meiotic recombination hotspot activation. S. pombe has a number of different classes of meiotic hotspots, indicating that a single pathway does not confer hotspot activity throughout the genome. The M26-related hotspots are a particularly well characterised group of hotspots and details of the molecular activation of M26-related hotspots are now coming to light. Moreover, genome-wide DNA array analysis has been applied to the question of meiotic recombination in this organism and we are now starting to get a picture of recombination hotspot distribution on a genome-wide scale.