Telomeres are heterochromatic domains composed of repetitive DNA (TTAGGG repeats) bound to an array of specialized proteins. Telomere maintenance is essential for protecting chromosome ends. Aberrations in telomere length have been implicated in cancer and aging. Telomeres and telomerase represent promising anticancer targets. However, 15% of cancer cells maintain their telomeres through alternative recombination-based mechanisms and previous analyses showed that recombination-based telomere maintenance can be activated after telomerase inhibition. So it is important to study how recombination-based telomere maintenance is activated. 
Fission yeast Schizosaccharomyces pombe is an excellent model organism to study telomere maintenance, because S. pombe is genetically tractable and most of the genes related to telomere maintenance are conserved in mammalian counterparts. We are interested in how telomere is maintained and what happen when telomere is deprotected. We are also interested in the mechanisms of DNA repair and chromosome segregation. Dr. Ueno lab has many publications about telomere research using S. pombe.
 The fission yeast Pot1 binds to single-stranded telomere DNA. Deletion of S. pombe pot1 results in the rapid loss of telomeric DNA and chromosome circularization. Based on this and other results, it is believed that Pot1 has two main functions: One is to recruit telomerase to telomere. The other is to protect telomere from degradation by unknown enzymes. Recently, Dr. Baumann lab reported that the double mutant between pot1 null and rqh1 null mutant is synthetically lethal (2). Rqh1 has helicase activity and is required for the suppression of homologous recombination throughout the genome. Interestingly, Dr. Ueno lab found that a double mutant between pot1 null and helicase-dead rqh1 mutant, in which lysine of position 547 in Rqh1 is mutated to alanine, is not synthetically lethality (1). The helicase-dead Rqh1mutant protein has no helicase activity in vitro. These facts indicate that Rqh1, but not the helicase activity of Rqh1, is required for the viability in the absence of Pot1. Dr. Ueno lab also found that a double mutant between pot1 null and helicase-dead rqh1 mutant is sensitive to microtubule drug, TBZ (1). Dr. Ueno lab also found that the synthetically lethality of a double mutant between pot1 null and rqh1 nullmutant can be suppressed by deletion of rad51 (3). Based on this and others data, we propose that Rqh1 inhibit circular chromosome dimmers by inhibiting crossing-over.
The chemical compounds that inhibit proper chromosome maintenance including DNA recombination, DNA damage checkpoint, chromosome segregation, and telomere protection, can be used as anti-cancer drugs. Dr. Ueno lab has created several mutants that could be used to identify inhibitor of proper chromosome maintenance in S. pombe. For example, telomeres in pot1D rqh1-hd double mutant are maintained by homologous recombination. The recombination intermediates are accumulated at telomere even in M phase and inhibit chromosome segregation, which make the pot1D rqh1-hd double mutant sensitive to microtubule drug tiabendazole, TBZ (1). Using this mutant and other mutants created in Ueno lab, we will develop new methods to screen chemical compounds, which will be used as anti-cancer drugs.    

References
(1) Mol. Cell. Biol. 2011. 31(3):495-506.
(2) Mol. Cell. 2008. 31(4):463-73.
(3) Mol. Cell. Biol. 2013. In press.