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, and its binding partner protein TRAX (translin-associated factor-X) are a paralogous pair of conserved proteins, which have been implicated in a broad spectrum of biological activities, including cell growth regulation, mRNA processing, spermatogenesis, neuronal development/function, genome stability regulation and carcinogenesis, although their precise role in some of these processes remains unclear. Furthermore, translin (with or without TRAX) has nucleic-acid-binding activity and it is apparent that controlling nucleic acid metabolism and distribution are central to the biological role(s) of this protein and its partner TRAX. More recently, translin and TRAX have together been identified as enhancer components of an RNAi (RNA interference) pathway in at least one organism and this might provide critical insight into the biological roles of this enigmatic partnership. In the present review we discuss the biological and the biochemical properties of these proteins that indicate that they play a central and important role in eukaryotic cell biology.

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.