Biology subjects

Cavka, I.

Publications and source records attributed to Cavka, I..

3 recordsLinked to original sources

bioRxiv2024

SpotMAX: a generalist framework for multi-dimensional automatic spot detection and quantification

The analysis of spot-like structures is a widespread task in microscopy-based cell biology. Existing solutions are typically specific to single applications and do not use multi-dimensional information from 5D datasets. Therefore, experimental scientists often resort to subjective manual annotation. Here, we present SpotMAX, a generalist AI-driven framework for automated spot detection and quantification. SpotMAX leverages the full scope of multi-dimensional datasets with an easy-to-use interface and an embedded framework for cell segmentation and tracking. SpotMAX outperforms state-of-the-art tools, and in some cases, even expert human annotators. We applied SpotMAX across diverse experimental questions, ranging from meiotic crossover events in C. elegans to mitochondrial DNA dynamics in S. cerevisiae and telomere length in mouse stem cells, leading to new biological insights. With its flexibility in integrating AI workflows, we anticipate that SpotMAX will become the standard for spot analysis in microscopy data. Source code: https://github.com/SchmollerLab/SpotMAX

cell biology↗

bioRxiv2024

Crossovers are regulated by a conserved and disordered synaptonemal complex domain

To ensure the accurate segregation of homologous chromosomes and enhance the genetic diversity in the progeny, meiosis depends on the formation of crossovers between homologous chromosomes. The number and distribution of these crossovers must be precisely regulated through crossover assurance and interference to prevent chromosome missegregation and genomic instability. Here we show that the regulation of crossovers depends on a disordered domain within the synaptonemal complex, which is highly conserved. This domain is located at the C-terminus of the central element protein SYP-4 in C. elegans. While not necessary for synapsis, the C-terminus of SYP-4 is crucial for both crossover assurance and interference. Although the SYP-4 C-terminus contains many potential phosphorylation sites, we found that phosphorylation is not the primary regulator of crossover events. Instead, we discovered that nine conserved phenylalanines recruit a pro-crossover factor predicted to be an E3 ligase and regulate the physical properties of the synaptonemal complex. We propose that this conserved and disordered domain plays a crucial role in maintaining the synaptonemal complex in an activated state to promote crossing-over. This activation allows the synaptonemal complex to regulate the number and distribution of crossovers along chromosomes, thereby protecting the genome for future generations.

cell biology↗

bioRxiv2023

Skp1 proteins are structural components of the synaptonemal complex in C. elegans

The synaptonemal complex (SC) is a hallmark of meiotic prophase that plays a crucial role in regulating crossovers between homologous chromosomes. Here, we demonstrate that two Skp1-related proteins in C. elegans, SKR-1 and SKR-2, serve as structural components of the SC, independent of their canonical functions within the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex. SKR-1 and SKR-2 localize to the central region of the SC, and synapsis requires their dimerization through a hydrophobic interface that overlaps with the binding sites for CUL-1 and F-box proteins. Using in vitro reconstitution and in vivo analysis of mutant proteins, we show that SKR proteins interact with the other SC proteins using their C-terminal helices to form a soluble complex, which likely represents a basic building block for SC assembly. Our findings demonstrate how conserved Skp1 proteins are repurposed as part of the SC and may provide insight into how synapsis is coupled to cell cycle progression.

cell biology↗