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Sites of strong Rec12/Spo11 binding in the fission yeast genome are associated with meiotic recombination and with centromeres

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Abstract

Meiotic recombination arises from Rec12/Spo11-dependent formation of DNA double-strand breaks (DSBs) and their subsequent repair. We identified Rec12-binding peaks across the Schizosaccharomyces pombe genome using chromatin immunoprecipitation after reversible formaldehyde cross-linking combined with whole-genome DNA microarrays. Strong Rec12 binding coincided with previously identified DSBs at the recombination hotspots ura4A, mbs1, and mbs2 and correlated with DSB formation at a new site. In addition, Rec12 binding corresponded to eight novel conversion hotspots and correlated with crossover density in segments of chromosome I. Notably, Rec12 binding inversely correlated with guanine–cytosine (GC) content, contrary to findings in Saccharomyces cerevisiae. Although both replication origins and Rec12-binding sites preferred AT-rich gene-free regions, they seemed to exclude each other. We also uncovered a connection between binding sites of Rec12 and meiotic cohesin Rec8. Rec12-binding peaks lay often within 2.5 kb of a Rec8-binding peak. Rec12 binding showed preference for large intergenic regions and was found to bind preferentially near to genes expressed strongly in meiosis. Surprisingly, Rec12 binding was also detected in centromeric core regions, which raises the intriguing possibility that Rec12 plays additional roles in meiotic chromosome dynamics.

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Acknowledgments

We thank Hirofumi Aiba for the gpd1-E13 mutant, Andrea Ludin for writing the information retrieval programs to perform statistical analysis, Chris Penkett for help with the ArrayExpress submission, and Eva Heiniger and Silvia Steiner for construction of the rec6Δ and rec14Δ strains. We also thank Gareth Cromie and Gerry Smith, HCRC Seattle, for communication of results ahead of publication. The study was supported by the Swiss National Science Foundation to JK, and by Cancer Research UK [CUK], Grant No. C9546/A6517 to JB. KL was supported by a Marie-Heim-Vögtlin fellowship.

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Ludin, K., Mata, J., Watt, S. et al. Sites of strong Rec12/Spo11 binding in the fission yeast genome are associated with meiotic recombination and with centromeres. Chromosoma 117, 431–444 (2008). https://doi.org/10.1007/s00412-008-0159-3

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