Biology subjects

Smolikove, S.

Publications and source records attributed to Smolikove, S..

3 recordsLinked to original sources

bioRxiv2024

Distinct intersecting pathways link homolog pairing to initiation of meiotic chromosome synapsis

Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and Synaptonemal Complex assembly (SC) at their interface. Here, we investigate on new factors that promote and coordinate these events during C. elegans meiosis. We identify BRA-2 (BMP Receptor Associated family member 2) as an interactor of HIM-17, previously shown to promote double-strand break formation. We found that loss of bra-2 specifically impairs synapsis licensing without affecting homologs recognition, SC maintenance or chromosome movement. Double mutant analysis revealed a previously unrecognized role for HIM-17 in promoting homolog pairing under dysfunctional SC assembly, without perturbing nuclear envelope recruitment of factors required for chromosome movement. We provide evidence that bra-2 and him-17 act in distinct pathways, exerting partially redundant functions in SC licensing, as well as separable roles in regulating homologs pairing. Altogether, our findings unveil novel mechanisms that ensure stabilization of homologous chromosome interaction via SC licensing upon homology assessment.

cell biology↗

bioRxiv2020

RPA complexes in Caenorhabditis elegans meiosis; unique roles in replication, meiotic recombination and apoptosis

Replication Protein A (RPA) is critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) that form a trimeric complex critical for viability. The Caenorhabditis elegans genome encodes for RPA-1, RPA-2 and an RPA-2 paralog RPA-4. In our analysis, we determine that RPA-2 is critical for germline replication, and normal repair of meiotic DSBs. Interestingly, RPA-1 but not RPA-2 is essential for replication, contradictory to what is seen in other organisms, that require both subunits. In the germline, both RPA-1/2 and RPA-1/4 complexes form, but RPA-1/4 is less abundant and its formation is repressed by RPA-2. While RPA-4 does not participate in replication or recombination, we find that RPA-4 inhibit RAD-51 filament formation and promotes apoptosis on a subset of damaged nuclei. Altogether these findings point to sub-functionalization and antagonistic roles of RPA complexes in C. elegans.

genetics↗

bioRxiv2020

Recruitment of MRE-11 to complex DNA damage is modulated by meiosis-specific chromosome organization

DNA double-strand breaks (DSBs) are one of the most dangerous assaults on the genome, and yet their natural and programmed production are inherent to life. When DSBs arise close together (clustered) they are particularly deleterious, and their repair may require an altered form of the DNA damage response. Our understanding of how clustered DSBs are repaired in the germline is unknown. Using UV laser microirradiation, we examine early events in the repair of clustered DSBs in germ cells within whole, live, Caenorhabditis elegans. We use precise temporal resolution to show how the recruitment of MRE-11 to complex damage is regulated, and that clustered DNA damage can recruit proteins from various repair pathways. Abrogation of non-homologous end joining or COM-1 attenuates the recruitment of MRE-11 through distinct mechanisms. The synaptonemal complex plays both positive and negative regulatory roles in these mutant contexts. These findings together indicate that MRE-11 is regulated by modifying its accessibility to chromosomes.

genetics↗