Ivana Cavka

All Publications

• Multi-step implementation of meiotic crossover patterning. bioRxiv : the preprint server for biology Čavka, I., Woglar, A., Wu, Y. L., Durmus, E. B., Sloat, L., Gros, A., Piñeiro López, C., Hecht, F., Villeneuve, A. M., Ries, J., Köhler, S. 2025

  Abstract

  Crossover formation during meiosis is a tightly controlled process in which genetic information is exchanged between homologous chromosomes to increase the diversity of the progeny. In this process, an excess of double-strand breaks is introduced, but only a limited subset is ultimately processed into crossovers. Imbalances in the distribution of crossovers can lead to errors in chromosome segregation, with devastating consequences on the health of the progeny. However, the selection of which breaks are designated to become crossovers is still poorly understood, as both its timing and the ultimate molecular mechanisms are under debate. Here, we used 3D dual-color single-molecule localization microscopy and real-time confocal imaging, combined with advanced image analysis, to investigate the timing and mechanism of crossover designation in C. elegans. We show that meiotic crossover patterning is not established by a single decision point but depends on a dynamic, multi-layered regulation process. An initial, early selection process restricts potential crossovers to a small subset of double-strand break sites that already exhibit basic patterning features, including assurance and interference. A second, later step fine-tunes this pattern to ultimately ensure genome integrity and promote accurate chromosome segregation. Real-time imaging reveals that although the full process takes more than seven hours, key molecular events occur within minutes, highlighting how rapid local dynamic changes can give rise to an overall slow but extremely robust crossover regulation program.

  View details for DOI 10.1101/2025.11.12.687980

  View details for PubMedID 41292815

  View details for PubMedCentralID PMC12642587

• Bloom helicase contributes to successful crossover formation with both catalytic and structural roles in Caenorhabditis elegans meiosis NUCLEIC ACIDS RESEARCH Geetha, S., Cavka, I., Dello Stritto, M., Graf, A., Macha, T., Krakolinig, H., Kohler, S., Jantsch, V. 2025; 53 (19)

  Abstract

  Crossover (CO)-biased repair of meiotic DNA double-strand breaks is essential for proper chromosome segregation. However, only a subset of programmed induced DSBs is repaired as COs, while the rest is processed into non-COs. The Bloom-Topoisomerase 3-RMI1/2 complex is well documented to disassemble joint recombination intermediates into non-COs, but its pro-CO activities are less well understood. Here, we investigate how the pro-CO activities of the Caenorhabditis elegans Bloom helicase ortholog HIM-6 contribute to meiotic recombination by studying a catalytically inactive mutant. We show that HIM-6 helicase activity is required to provide a continuous flux of substrates for CO formation, probably via its unwinding activities, and that a structural role is sufficient to channel intermediates into the preferred pathway to generate correctly positioned COs. We provide evidence that the catalytic activity of Bloom helicase influences the geometry of the joint DNA molecules (double Holliday junctions (dHJ)). Localization of the signal for the dHJ-stabilizing complex MutSγ was more restricted, and epistasis experiments suggest that an altered geometry impedes the efficient processing of joint DNA molecules to generate CO-biased cleavage products.

  View details for DOI 10.1093/nar/gkaf1030

  View details for Web of Science ID 001597469800001

  View details for PubMedID 41123207

  View details for PubMedCentralID PMC12541369

• Crossovers are regulated by a conserved and disordered synaptonemal complex domain NUCLEIC ACIDS RESEARCH Neves, A., Cavka, I., Rausch, T., Koehler, S. 2025; 53 (4)

  Abstract

  During meiosis, the number and distribution of crossovers (COs) must be precisely regulated through CO assurance and interference to prevent chromosome missegregation and genomic instability in the progeny. Here we show that this regulation of COs depends on a disordered and conserved domain within the synaptonemal complex (SC). This domain is located at the C-terminus of the central element protein SYP-4 in Caenorhabditis elegans. While not necessary for synapsis, the C-terminus of SYP-4 is crucial for both CO assurance and interference. Although the SYP-4 C-terminus contains many potential phosphorylation sites, we found that phosphorylation is not the primary regulator of CO events. Instead, we discovered that nine conserved phenylalanines are required to recruit a pro-CO factor predicted to be an E3 ligase and regulate the physical properties of the SC. We propose that this conserved and disordered domain plays a crucial role in maintaining the SC in a state that allows transmitting signals to regulate CO formation. While the underlying mechanisms remain to be fully understood, our findings align with existing models suggesting that the SC plays a critical role in determining the number and distribution of COs along chromosomes, thereby safeguarding the genome for future generations.

  View details for DOI 10.1093/nar/gkaf095

  View details for Web of Science ID 001424370500004

  View details for PubMedID 39964475

  View details for PubMedCentralID PMC11833701