Biomedical subjects

Sergio Moreno

Publications and source records attributed to Sergio Moreno.

4 recordsLinked to original sources

PubMed2025

Nrm1 is a bistable switch connecting cell cycle progression to transcriptional control.

Entry into the cell cycle requires activation of G1 cyclin-dependent kinases (CDKs) and the G1/S transcriptional program. In fission yeast, the MBF complex is the main transcription factor driving early cell-cycle gene expression. MBF-dependent transcription is activated in metaphase and repressed at the end of S phase by a feedback loop involving the cyclin Cig2 and co-repressors Nrm1 and Yox1. While replicative stress inactivates Yox1 via phosphorylation, the mechanism that activates MBF during an unperturbed cell cycle remains unclear. Here, we identify Nrm1 as the key target of cell cycle regulation in a two-step control mechanism. First, CDK1 phosphorylates Nrm1 in metaphase, leading to its release-along with Yox1-from chromatin. Second, unphosphorylated Nrm1, generated either by dephosphorylation or de novo synthesis, is degraded during anaphase, preventing its re-association with MBF until the end of the next S phase. Together, these parallel pathways create a precisely timed window of MBF activation, ensuring proper cell cycle progression and preserving genomic stability.

Schizosaccharomyces↗

PubMed2003

Systematic functional analysis of the Caenorhabditis elegans genome using RNAi.

A principal challenge currently facing biologists is how to connect the complete DNA sequence of an organism to its development and behaviour. Large-scale targeted-deletions have been successful in defining gene functions in the single-celled yeast Saccharomyces cerevisiae, but comparable analyses have yet to be performed in an animal. Here we describe the use of RNA interference to inhibit the function of approximately 86% of the 19,427 predicted genes of C. elegans. We identified mutant phenotypes for 1,722 genes, about two-thirds of which were not previously associated with a phenotype. We find that genes of similar functions are clustered in distinct, multi-megabase regions of individual chromosomes; genes in these regions tend to share transcriptional profiles. Our resulting data set and reusable RNAi library of 16,757 bacterial clones will facilitate systematic analyses of the connections among gene sequence, chromosomal location and gene function in C. elegans.

Animals↗

PubMed2003

Regulation of meiotic progression by the meiosis-specific checkpoint kinase Mek1 in fission yeast.

During the eukaryotic cell cycle, accurate transmission of genetic information to progeny is ensured by the operation of cell cycle checkpoints. Checkpoints are regulatory mechanisms that block cell cycle progression when key cellular processes are defective or chromosomes are damaged. During meiosis, genetic recombination between homologous chromosomes is essential for proper chromosome segregation at the first meiotic division. In response to incomplete recombination, the pachytene checkpoint (also known as the meiotic recombination checkpoint) arrests or delays meiotic cell cycle progression, thus preventing the formation of defective gametes. Here, we describe a role for a meiosis-specific kinase, Mek1, in the meiotic recombination checkpoint in fission yeast. Mek1 belongs to the Cds1/Rad53/Chk2 family of kinases containing forkhead-associated domains, which participate in a number of checkpoint responses from yeast to mammals. We show that defects in meiotic recombination generated by the lack of the fission yeast Meu13 protein lead to a delay in entry into meiosis I owing to inhibitory phosphorylation of the cyclin-dependent kinase Cdc2 on tyrosine 15. Mutation of mek1(+) alleviates this checkpoint-induced delay, resulting in the formation of largely inviable meiotic products. Experiments involving ectopic overexpression of the mek1(+) gene indicate that Mek1 inhibits the Cdc25 phosphatase, which is responsible for dephosphorylation of Cdc2 on tyrosine 15. Furthermore, the meiotic recombination checkpoint is impaired in a cdc25 phosphorylation site mutant. Thus, we provide the first evidence of a connection between an effector kinase of the meiotic recombination checkpoint and a crucial cell cycle regulator and present a model for the operation of this meiotic checkpoint in fission yeast.

Amino Acid Sequence↗

PubMed2002

Mental models in deductive reasoning.

We report research investigating the role of mental models in deduction. The first study deals with conjunctive inferences (from one conjunction and two conditional premises) and disjunctive inferences (from one disjunction and the same two conditionals). The second study examines reasoning from multiple conditionals such as: If e then b; If a then b; If b then c; What follows between a and c? The third study addresses reasoning from different sorts of conditional assertions, including conditionals based on if then, only if, and unless. The paper also presents research on figural effects in syllogistic reasoning, on the effects of structure and believability in reasoning from double conditionals, and on reasoning from factual, counterfactual, and semifactual conditionals. The findings of these studies support the model theory, pose some difficulties for rule theories, and show the influence on reasoning of the linguistic structure and the semantic content of problems.

Cognition↗