Biology subjects

Perez-Martinez, L.

Publications and source records attributed to Perez-Martinez, L..

4 recordsLinked to original sources

bioRxiv2024

Fecal Virome Transplantation (FVT) from healthy humans remodels the gut bacteriome and virome and reduces metabolic syndrome in mice

AbstractThe gut microbiome regulates host processes, including metabolism, and comprises viruses, archaea, fungi, protists, and bacteria. However, previous studies have primarily focused on the bacterial components of the microbiome. This study conducted cross-infection experiments by fecal virome transplantation (FVT) to examine the impact of virus-like particles (VLPs) from normal-weight individuals on bacterial and virome diversity and metabolic changes in mice. We found that FVT significantly restored glucose tolerance in mice, even though they were maintained on a high-fat diet (HFD). Shotgun metagenomics and 16s profiling confirmed that FVT shifted gut bacterial and viral richness and diversity, resulting in several differentially abundant bacteria and phages. The abundance of Akkermansia muciniphila decreased significantly after FVT, remained low until the end of the experiment (week 17), and correlated with a decreased glucose tolerance. On the other hand, there was a significant increase in Allobaculum and Coprococcus at weeks 10 and 17 post-FVT. The abundance of Allobaculum correlated with an increased glucose tolerance, indicating a beneficial hypoglycemic effect on the mice inoculated with VLPs. We also found an increased virome diversity at week 17, while richness was similar to the one before FVT. The study provides a proof of concept for the efficacy of FVT from human donors to mice, improving glucose tolerance by altering the gut microbiota and virome despite maintaining a HFD. Overall, our results suggest that trans-kingdom interactions between the virome and bacteriome from humans could be translated to mice as a study model.

microbiology↗

bioRxiv2023

Msc1 is a nuclear envelope protein that reinforces DNA repair in late mitosis.

Precise double-strand break (DSB) repair is paramount for genome stability. Homologous recombination (HR) repairs DSBs when cyclin-dependent kinase (CDK) activity is high, which correlates with the availability of the sister chromatid as a template. However, anaphase and telophase are paradoxical scenarios since high CDK favors HR despite sister chromatids being no longer aligned. To identify factors specifically involved in DSB repair in late mitosis, we have undertaken comparative proteomics in Saccharomyces cerevisiae and found that Msc1, a poorly characterized nuclear envelope protein, is significantly enriched upon both random and guided DSBs. We further show that {Delta}msc1 is more sensitive to DSBs in late mitosis, and has a delayed repair of DBSs, as indicated by increased Rad53 hyperphosphorylation, fewer Rad52 repair factories, and slower HR completion. We discuss how Msc1 may favor the formation of Rad52 factories and the timely completion of HR before cytokinesis.

molecular biology↗

bioRxiv2023

Exposure to an enriched environment improves colonic epithelial barrier integrity and attenuates mouse experimental colitis by modulating a Myc-driven gene regulatory network

Withdrawal StatementThe authors have withdrawn their manuscript owing to erroneous labeling in two figures that have recently come to light. Experiments aiming to confirm the data presented are underway. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

immunology↗

bioRxiv2020

Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence

Telomeres adopt a lariat conformation and hence, engage in long and short distance intra-chromosome interactions. Budding yeast telomeres were proposed to fold back into subtelomeric regions, but a robust assay to quantitatively characterize this structure has been lacking. Therefore, it is not well understood how the interactions between telomeres and non-telomeric regions are established and regulated. We employ a telomeric chromosome conformation capture (Telo-3C) approach to directly analyze telomere folding and its maintenance in S. cerevisiae. We identify the histone modifiers Sir2, Sin3 and Set2 as critical regulators for telomere folding, which suggests that a distinct telomeric chromatin environment is a major requirement for the folding of yeast telomeres. We demonstrate that telomeres are not folded when cells enter replicative senescence, which occurs independently of short telomere length. Indeed, Sir2, Sin3 and Set2 protein levels are decreased during senescence and their absence may thereby prevent telomere folding. Additionally, we show that the homologous recombination machinery, including the Rad51 and Rad52 proteins, as well as the checkpoint component Rad53 are essential for establishing the telomere fold-back structure. This study outlines a method to interrogate telomere-subtelomere interactions at a single unmodified yeast telomere. Using this method, we provide insights into how the spatial arrangement of the chromosome end structure is established and demonstrate that telomere folding is compromised throughout replicative senescence. Author summaryTelomeres are the protective caps of chromosome ends and prevent the activation of a local DNA damage response. In many organisms, telomeres engage in a loop-like structure which may provide an additional layer of end protection. As we still lack insight into the regulation of the folded telomere structure, we used budding yeast to establish a method to measure telomere folding and then study the genetic requirements for its establishment. We found that cells require the homologous recombination machinery as well as components of the DNA damage checkpoint to successfully establish a folded telomere. Through the deletion of telomerase in budding yeast, we investigated how telomere folding was regulated during replicative senescence, a process that occurs in the majority of telomerase negative human cells. During senescence, telomeres gradually shorten and erode until cells stop dividing which is a potent tumor suppressor and prevents unscheduled growth of potential cancer cells. We found, that the folded telomere structure is compromised as part of the cellular senescence response, but not due to telomere shortening per se. We think, that an altered telomeric chromatin environment during senescence is important to maintain an open state - which may be important for signaling or for repair.

genetics↗