BioEssays最新文献

Life on Earth has evolved as a series of evolutionary transitions, during which lower-level units merged to form a new and more complex higher-level entity. Besides few canonical examples, many life forms exist for which it remains unclear whether or not they are about to complete the transition. This paucity of mechanistic understanding is likely due to an overemphasis on few model systems and a lack of criteria to compare disparate biological units. Here, we aim at filling this gap by proposing a new framework to classify different forms of biological organization, which considers two fundamental aspects: (i) the physiological component and (ii) the evolutionary component. Categorizing different biological units according to whether and how these aspects are represented yields six types of structural organization. Our framework allows to compare different organizational forms, and, in this way, provide insight into the evolutionary processes giving rise to these arrangements.

In well-perfused tissues, interstitial composition resembles capillary plasma. Solid tumors break this norm because cancer cell proliferation outpaces vascular expansion, leading to a diffusion-limited tumor microenvironment (TME) that is notably depleted of oxygen and enriched in acids. The magnitude of tumor acidosis; its chemical composition in terms of [CO₂] and [HCO₃⁻] (components of the major extracellular buffer); and its relationship with hypoxia are not intuitive to predict but important to know for designing experiments and contextualising results. We address these timely questions using mathematical models of a monolayer, spheroid, and poorly-perfused tissue. Our simulations suggest a physiologically realistic TME pH range of 6.7–7.4, reveal a prominence of hypercapnia, and indicate varying levels of HCO₃⁻ depletion or accumulation arising from fermentation and respiration, respectively. The trajectories of tumor hypoxia and acidosis depend on the balance between aerobic and anaerobic pathways, with important consequences on hypoxic signaling where many responses are pH-sensitive.

Accurate and timely genome replication is a universal feature of living organisms and a prerequisite for cell proliferation. In eukaryotes, genomic DNA replication initiates in two steps, origin licensing and origin firing, reflecting the loading and activation of the MCM replicative helicase motor on origin DNA. Biochemical reconstitution of these steps in the budding yeast model system signified a major advance towards understanding the molecular and structural details of eukaryotic replication initiation events. With recent successes in reconstituting origin licensing with purified human proteins, a mechanistic picture is beginning to emerge on how DNA replication initiates in higher eukaryotes and how it deviates from the paradigms established in budding yeast. In this review, we highlight similarities and differences in licensing mechanisms between yeast and metazoa.

Recapitulation of the nuclear auxin response pathway in yeast led to the hypothesis that corepressors prime loci for rapid bursts of transcription. Specifically, the TPL corepressor, which inhibits transcription in the absence of auxin, interfaces with Mediator and core components of the transcription pre-initiation complex (PIC). Once auxin is perceived, RNA Pol-II is likely to essentially displace TPL, allowing for rapid transcription initiation (and likely re-firing). Here, we present the current evidence supporting the role of TPL-type corepressors in multiple levels of transcriptional control, including modulation of regulatory transcription factor activity, interactions between cis-elements and the core promoter, and in organizing multiple loci within the nucleoplasm. We also highlight critical areas for future investigations.

The synaptonemal complex (SC), a hallmark of meiosis, is a zipper-like protein assembly that links homologous chromosomes to regulate their recombination and segregation. With its characteristic ladder-like structure bridging paired homologs, the SC possesses unique biochemical and biophysical properties that influence both the number and distribution of crossovers. Although its ultrastructure is strikingly similar across eukaryotes, the molecular mechanisms underlying SC assembly and regulation are remarkably diverse, reflecting both conserved principles and evolutionary innovation. In this review, we synthesize current knowledge of the pathways that promote homologous synapsis across diverse model organisms. We focus on how synapsis initiation is coordinated with other meiotic processes, particularly homolog pairing and recombination, and highlight emerging themes, including the spatial and temporal regulation of SC assembly and the conserved molecular modules that couple SC assembly to recombination sites.