Population genomics ofSaccharomyces cerevisiaehuman isolates: passengers, colonizers, invaders.

The quest for the ecological niches ofSaccharomyces cerevisiaeranged from wineries to oaks and more recently to the gut of Crabro Wasps. Here we propose the role of the human gut in shapingS. cerevisiaeevolution, presenting the genetic structure of a previously unknown population of yeasts, associated with Crohn?s disease, providing evidence for clonal expansion within human?s gut. To understand the role of immune function in the human-yeast interaction we classified strains according to their immunomodulatory properties, discovering a set of genetically homogeneous isolates, capable of inducing anti-inflammatory signals via regulatory T cells proliferation, and on the contrary, a positive association between strain mosaicism and ability to elicit inflammatory, IL-17 driven, immune responses. The approach integrating genomics with immune phenotyping showed selection on genes involved in sporulation and cell wall remodeling as central for the evolution ofS. cerevisiaeCrohn?s strains from passengers to commensals to potential pathogens.

Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death

CENP-C, one of the few known intrinsic proteins of the human centromere, is thought to play structural as well as regulatory roles crucial to proper chromosome segregation and mitotic progression. To further define the functions of CENP-C throughout the cell cycle we have used the yeast interaction trap to identify proteins with which it interacts. One specific CENP-C interactor, which we have named HDaxx, was characterized in detail and found to be homologous to murine Daxx, a protein identified through its ability to bind the death domain of Fas (CD95). The interaction between CENP-C and HDaxx is mediated by the amino-terminal 315 amino acids of CENP-C and the carboxyl-terminal 104 amino acids of HDaxx. This region of Daxx is responsible for binding to death domains of several apoptosis signalling proteins. The biological significance of the interaction between CENP-C and HDaxx was confirmed by immunofluorescence colocalization of these two proteins at discrete spots in the nuclei of some interphase HeLa cells. We discuss the functional implications of the interphase-restricted association of HDaxx with centromeres.