Biology subjects

Brun, C.

Publications and source records attributed to Brun, C..

3 recordsLinked to original sources

bioRxiv2018

Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4

Programmed formation of DNA double strand breaks (DSBs) initiates the meiotic homologous recombination pathway. This pathway allows homologous chromosomes to find each other and the formation of crossing overs, the products of reciprocal exchanges, which are required for proper chromosome segregation at the first meiotic division. Meiotic DSBs are catalyzed by Spo11 that forms a complex with a second subunit, TopoVIBL, and mediates a DNA type II topoisomerase-like cleavage. Several other proteins are essential for meiotic DSB formation, including three evolutionarily conserved proteins first identified in Saccharomyces cerevisiae (Mer2, Mei4 and Rec114). These three S. cerevisiae proteins and their mouse orthologs (IHO1, MEI4 and REC114) co-localize on the axes of meiotic chromosomes, and mouse IHO1 and MEI4 are essential for meiotic DSB formation. Here, we show that mouse Rec114 is required for meiotic DSB formation. Moreover, MEI4 forms a complex with REC114 and IHO1 in mouse spermatocytes, consistent with cytological observations. We then demonstrated in vitro the formation of a stable complex between REC114 C-terminal domain and MEI4 N-terminal domain. We further determine the structure of REC114 N-terminal domain that revealed similarity with Pleckstrin Homology domains and its property to dimerize. These analyses provide direct insights into the architecture of these essential components of the meiotic DSB machinery.

molecular biology↗

bioRxiv2018

Generation of a versatile BiFC ORFeome library for analyzing protein-protein interactions in live Drosophila

Transcription factors achieve specificity by establishing intricate interaction networks that will change depending on the cell context. Capturing these interactions in live condition is however a challenging issue that requires sensitive and non-invasive methods. We present a set of fly lines, called \"multicolor BiFC library\", which covers most of the Drosophila transcription factors for performing Bimolecular Fluorescence Complementation (BiFC). The multicolor BiFC library can be used to probe binary or tripartite interactions and is compatible for large-scale interaction screens. The library can also be coupled with established Drosophila genetic resources to analyze interactions in the developmentally relevant expression domain of each protein partner. We provide proof of principle experiments of these various applications, using Hox proteins in the live Drosophila embryo as a case study. Overall this novel collection of ready-to-use fly lines constitutes an unprecedented genetic toolbox for the identification and analysis of protein-protein interactions in vivo.

genomics↗

bioRxiv2016

Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence factors

F. nucleatum is a gram-negative anaerobic species residing in the oral cavity and implicated in several inflammatory processes in the human body. Although F. nucleatum abundance is increased in inflammatory bowel disease subjects and is prevalent in colorectal cancer patients, the causal role of the bacterium in gastrointestinal disorders and the mechanistic details of host cell functions subversion are not fully understood.\n\nWe devised a computational strategy to identify putative secreted F. nucleatum proteins (FusoSecretome) and to infer their interactions with human proteins based on the presence of host molecular mimicry elements. FusoSecretome proteins share similar features with known bacterial virulence factors thereby highlighting their pathogenic potential. We show that they interact with human proteins that participate in infection-related cellular processes and localize in established cellular districts of the host-pathogen interface. Our network-based analysis identified 31 functional modules in the human interactome preferentially targeted by 138 FusoSecretome proteins, among which we selected 26 as main candidate virulence proteins, representing both putative and known virulence proteins. Finally, 6 of the preferentially targeted functional modules are implicated in the onset and progression of inflammatory bowel diseases and colorectal cancer.\n\nOverall, our computational analysis identified candidate virulence proteins potentially involved in the F. nucleatum - human cross-talk in the context of gastrointestinal diseases.

bioinformatics↗