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Genome-wide measurements of transcriptional activity in bacteriaindicate that the transcription of successive genes is stronglycorrelated beyond the scale of operons. I will present an analysis ofhundreds of bacterial genomes to identify supra-operonic segments ofgenes that are proximal in a large number of genomes. The syntenysegments that it yields correspond to genomic units of strongtranscriptional co-expression. Structurally, the segments containoperons with specific relative orientations (co-directional ordivergent) and nucleoid-associated proteins are found to bind at theirboundaries. Functionally, operons inside a same segment are highlyco-expressed even in the absence of regulatory factors at theirpromoter regions. Remote operons along DNA can also be co-expressed iftheir segments share a transcriptional or sigma factor, withoutrequiring these factors to bind directly to the promoters of theoperons. As evidence that these results apply across the bacterialkingdom, I will demonstrate them both in the Gram-negative bacteriumEscherichia coli and in the Gram-positive bacterium Bacillus subtilis.The underlying process that we propose involves only…

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Meiotic recombination is initiated in diploid germline cells by the programmed introduction of hundreds of DNA double strand breaks (DSBs) along chromosomes. These DSBs are then repaired by homologous recombination, one of the outcomes being the crossovers, where homologous chromosome arms are exchanged. Meiotic crossing overs are necessary for gamete viability. Errors in meiotic crossover formation are the major source of aneuploidies leading to sterility and chromosomal diseases such as Trisomy 21. Meiotic recombination is also an important source of genetic diversity, generated through the crossovers that shuffle existing combination of alleles, but also through the unidirectional events called conversions that take place at all meiotic recombination sites. We have recently uncovered a new function of the poorly characterized mismatch repair complex, MutLbeta (Mlh1-Mlh2 in budding yeast), in meiotic recombination. We found that it interacts with recombination proteins to regulate their activity and limit the extent of genetic material exchanged between homologs…

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Cross-linking mass spectrometry (XL-MS) is increasingly used for structural characterization of multi-subunit protein complexes. Chemical cross-linking captures conformational heterogeneity, which typically results in conflicting cross-links that cannot be satisfied in a single model, making detailed modeling a challenging task. Here we introduce an automated modeling method dedicated to large protein assemblies that (i) uses a form of spatial restraints that realistically reflects the distribution of experimentally observed cross-linked distances, (ii) automatically deals with ambiguous and / or conflicting cross-links and identifies alternative conformations within a Bayesian framework, (iii) allows subunit structures to be flexible during conformational sampling. We demonstrate the power of our method by testing it on known structures and available cross-linking data. We cross-linked and modeled  the 17-subunit yeast RNA polymerase III at atomic resolution. The resulting model agrees remarkably well with recently published cryo-electron microscopy structures and provides additional insights into the polymerase structure.