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The ade6-M26 allele of Schizosaccharomyces pombe creates a well-defined meiotic recombination hot spot that requires a specific sequence, 5'-ATGACGT-3', and the Atf1*Pcr1 transcription factor for activity. We find that M26 stimulates the formation of meiosis-specific double-strand DNA breaks at multiple sites surrounding M26. Like hot spot activity, breakage requires the M26 heptamer, Pcr1, and the general recombination factor Rec12. When the M26 heptamer is moved to new positions within ade6, new break sites are observed spanning approximately 0.5-2 kb around the moved heptamer. Break frequency is strongly correlated with recombination frequency for these alleles. The occurrence of breaks at M26 suggests mechanistic similarities to hot spots in the distantly related yeast Saccharomyces cerevisiae.

DNA breakage is intimately associated with meiotic recombination in the fission yeast Schizosaccharomyces pombe. Sites of prominent DNA breakage were found approximately 25 to approximately 200 kb apart in the genomic regions surveyed. We examined in detail a 501 kb region of chromosome I and found six sites, or tight clusters of sites, at which approximately 2%-11% of the DNA accumulated breaks in a rad50S mutant. In contrast to the discrete, widely spaced distribution of prominent break sites, recombination in this region was more uniformly distributed (0.7-1.6 cM/10 kb) whether the genetic interval tested contained no, one, or more such sites. We infer that although recombination depends upon DNA breakage, recombination often occurs remote from these sites (tens of kilobases away); we discuss mechanisms by which this may occur.

BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery.