Publications by authors named "John Weir"

Programmed DNA double-strand break (DSB) formation is a crucial feature of meiosis in most organisms. DSBs initiate recombination-mediated linking of homologous chromosomes, which enables correct chromosome segregation in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors.

View Article and Find Full Text PDF

Meiotic recombination, a cornerstone of eukaryotic diversity and individual genetic identity, is essential for the creation of physical linkages between homologous chromosomes, facilitating their faithful segregation during meiosis I. This process requires that germ cells generate controlled DNA lesions within their own genome that are subsequently repaired in a specialised manner. Repair of these DNA breaks involves the modulation of existing homologous recombination repair pathways to generate crossovers between homologous chromosomes.

View Article and Find Full Text PDF

Programmed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood.

View Article and Find Full Text PDF

Teleost fish of the genus Danio are excellent models to study the genetic and cellular bases of pigment pattern variation in vertebrates. The two sister species Danio rerio and Danio aesculapii show divergent patterns of horizontal stripes and vertical bars that are partly caused by the divergence of the potassium channel gene kcnj13. Here, we show that kcnj13 is required only in melanophores for interactions with xanthophores and iridophores, which cause location-specific pigment cell shapes and thereby influence colour pattern and contrast in D.

View Article and Find Full Text PDF

Crossing over between homologs is critical for the stable segregation of chromosomes during the first meiotic division. Saccharomyces cerevisiae Mer3 (HFM1 in mammals) is a SF2 helicase and member of the ZMM group of proteins, that facilitates the formation of the majority of crossovers during meiosis. Here, we describe the structural organisation of Mer3 and using AlphaFold modelling and XL-MS we further characterise the previously described interaction with Mlh1-Mlh2.

View Article and Find Full Text PDF
Article Synopsis
  • - Successful meiosis I relies on proper linkage of homologous chromosomes, primarily achieved through crossovers generated by meiotic recombination, which modifies standard DNA repair processes.
  • - DNA helicases play a crucial role in this process by coupling nucleic acid binding and hydrolysis to alter DNA and protein-DNA substrates necessary for crossover formation.
  • - The review examines the current understanding of meiotic helicases, their interactions, and how regulatory modifications affect their function during meiosis I, emphasizing their molecular structure and mechanisms.
View Article and Find Full Text PDF

Flagellin, the protein subunit of the bacterial flagellum, stimulates the innate immune receptor Toll-like receptor 5 (TLR5) after pattern recognition or evades TLR5 through lack of recognition. This binary response fails to explain the weak agonism of flagellins from commensal bacteria, raising the question of how TLR5 response is tuned. Here, we screened abundant flagellins present in metagenomes from human gut for both TLR5 recognition and activation and uncovered a class of flagellin-TLR5 interaction termed silent recognition.

View Article and Find Full Text PDF

For meiosis I, homologous chromosomes must be paired into bivalents. Maintenance of homolog conjunction in bivalents until anaphase I depends on crossovers in canonical meiosis. However, instead of crossovers, an alternative system achieves homolog conjunction during the achiasmate male meiosis of Drosophila melanogaster.

View Article and Find Full Text PDF
Article Synopsis
  • Fire refugia and patchiness are vital for conserving fire-sensitive species and enhancing biodiversity in fire-prone areas.
  • Large herbivores, by altering vegetation, can reduce wildfire risk and may help sustain these sensitive species.
  • An experiment studying Wyoming big sagebrush revealed that areas with herbivores had lower fire intensity and spread, highlighting their role in creating safe zones for plants during wildfires.
View Article and Find Full Text PDF
Article Synopsis
  • In meiosis, the formation of DNA double-strand breaks (DSBs) by the protein Spo11 kickstarts recombination and is essential for proper chromosome segregation.
  • Research focuses on Mer2, a key factor in the DSB machinery, showing it interacts with histone reader Spp1 and nucleosomes to help tether DSB factors to chromatin.
  • The study identifies a crucial conserved region within Mer2 that interacts with the DSB factor Mre11, positioning Mer2 as a central player in coordinating essential protein complexes necessary for initiating meiotic recombination.
View Article and Find Full Text PDF

As effects of climate change intensify, there is a growing need to understand the thermal properties of landscapes and their influence on wildlife. A key thermal property of landscapes is vegetation structure and composition. Management approaches can alter vegetation and consequently the thermal landscape, potentially resulting in underappreciated consequences for wildlife thermoregulation.

View Article and Find Full Text PDF

The successful production of recombinant protein for biochemical, biophysical, and structural biological studies critically depends on the correct expression organism. Currently, the most commonly used expression organisms for structural studies are Escherichia coli (~70% of all PDB structures) and the baculovirus/ insect cell expression system (~5% of all PDB structures). While insect cell expression is frequently successful for large eukaryotic proteins, it is relatively expensive and time-consuming compared to E.

View Article and Find Full Text PDF
Article Synopsis
  • Pch2 is a specialized protein essential for meiosis, interacting with Orc1, a component of the ORC complex involved in DNA replication.
  • This study reveals that Pch2 forms a direct connection with ORC during a specific stage of meiosis, indicating a complex relationship in chromosomal processes that goes beyond mere association with DNA origins.
  • The findings suggest that the cooperation between Orc1 and Pch2 in meiosis can occur independently of the usual binding of ORC to DNA replication sites, highlighting unique roles for these proteins in meiotic function.
View Article and Find Full Text PDF
Article Synopsis
  • - The study investigates how landowners and fire professionals view the risks linked to prescribed burning, despite its effectiveness in managing ecosystems.
  • - Data was gathered from prescribed fire professionals across 14 Southern and Midwestern states, revealing that those more concerned about safety and weather perceive higher risks, while experienced individuals tend to feel less risk.
  • - Sociodemographic factors like age and income do not significantly affect how risks are perceived, highlighting the importance of safety concerns and experience in decision-making regarding prescribed burns.
View Article and Find Full Text PDF
Article Synopsis
  • - The kinetochore is a complex structure formed by about thirty subunits that connect chromosomes to spindle microtubules, with CENP-A being a key histone variant located in the centromere.
  • - The CCAN (constitutive centromere associated network) consists of 16 subunits and serves as a stable bridge between CENP-A and the mikrotubule-binding KMN complex, which involves 10 subunits.
  • - Researchers successfully reconstituted an 11-subunit human CCAN core that links CENP-A and KMN, identifying important functional similarities between two complexes, CENP-OPQUR and NDC80, in their roles related to microtub
View Article and Find Full Text PDF

Extracorporeal membrane oxygenation has emerged as a treatment of choice for refractory hypoxemia in the intensive care unit. Severe hypoxemia unresponsive to conventional lung-protective mechanical ventilation could also occur in the operating room from severe bronchospasm, pulmonary contusions, or acute respiratory distress syndrome. We report a case of acute hypoxic respiratory failure in an adolescent with blunt chest trauma that was successfully managed with the intraoperative initiation of venovenous extracorporeal membrane oxygenation during the initial damage control surgery.

View Article and Find Full Text PDF

Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome.

View Article and Find Full Text PDF

Fire is a process that shaped and maintained most terrestrial ecosystems worldwide. Changes in land use and patterns of human settlement have altered fire regimes and led to fire suppression resulting in numerous undesirable consequences spanning individual species and entire ecosystems. Many obvious and direct consequences of fire suppression have been well studied, but several, albeit less obvious, costs of alteration to fire regimes on wildlife are unknown.

View Article and Find Full Text PDF
Article Synopsis
  • Chromosomes play a crucial role in carrying genetic material, and kinetochores help ensure their accurate transfer during cell division by connecting them to the mitotic spindle.
  • Kinetochores are complex structures made up of various protein subunits, with the inner kinetochore formed by a group of centromeric proteins (CCAN), and the outer kinetochore created by the KMN network, which binds microtubules.
  • The study reveals how a specific CCAN subcomplex (CHIKMLN) increases the binding selectivity for CENP-A nucleosomes, forming a strong link between CENP-A and microtubules, and sheds light on the organization and function of kinetocho
View Article and Find Full Text PDF

Kinetochores are macromolecular complexes built on a specialized chromatin domain called the centromere. Kinetochores provide a site of attachment for spindle microtubules during mitosis. They also control a cell cycle checkpoint, the spindle assembly checkpoint, which coordinates mitotic exit with the completion of chromosome alignment on the mitotic spindle.

View Article and Find Full Text PDF

The spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores to ensure accurate sister chromatid segregation during mitosis. The SAC members Bub1 and BubR1 are paralogs that underwent significant functional specializations during evolution. We report an in-depth characterization of the kinase domains of Bub1 and BubR1.

View Article and Find Full Text PDF

Fire is widely recognized as a critical ecological and evolutionary driver that needs to be at the forefront of land management actions if conservation targets are to be met. However, the prevailing view is that prescribed fire is riskier than other land management techniques. Perceived risks associated with the application of fire limits its use and reduces agency support for prescribed burning in the private sector.

View Article and Find Full Text PDF
Article Synopsis
  • Kinetochores are essential protein complexes that form on centromeres, binding to spindle microtubules to ensure proper chromosome separation during cell division.
  • The study focuses on CENP-C, a key component of the constitutive centromere-associated network (CCAN), which facilitates the assembly of kinetochores and connects centromeres with microtubules.
  • The researchers discovered that the PEST domain in CENP-C directly interacts with the CENP-HIKM subcomplex, revealing how CENP-C helps target other CCAN subunits to the kinetochore, highlighting its role in the overall assembly process.
View Article and Find Full Text PDF

The TRAMP complex is involved in the nuclear surveillance and turnover of noncoding RNAs and intergenic transcripts. TRAMP is associated with the nuclear exosome and consists of a poly(A)polymerase subcomplex (Trf4-Air2) and a helicase (Mtr4). We found that N-terminal low-complexity regions of Trf4 and Air2 bind Mtr4 in a cooperative manner.

View Article and Find Full Text PDF

Kinetochores, multi-subunit complexes that assemble at the interface with centromeres, bind spindle microtubules to ensure faithful delivery of chromosomes during cell division. The configuration and function of the kinetochore-centromere interface is poorly understood. We report that a protein at this interface, CENP-M, is structurally and evolutionarily related to small GTPases but is incapable of GTP-binding and conformational switching.

View Article and Find Full Text PDF