Biology subjects

Gordon, S. G.

Publications and source records attributed to Gordon, S. G..

5 recordsLinked to original sources

bioRxiv2022

Meiotic DNA exchanges are promoted by proximity to the synaptonemal complex

During meiosis, programmed double strand DNA breaks are repaired to form exchanges between the parental chromosomes called crossovers. Chromosomes lacking a crossover fail to segregate accurately into the gametes, leading to aneuploidy. Crossover formation requires the promotion of exchanges, rather than non-exchanges, as repair products. However, the mechanism underlying this meiosis-specific preference is not fully understood. Here, we study the regulation of meiotic sister chromatid exchanges in Caenorhabditis elegans by direct visualization. We find that a conserved chromosomal interface that promotes exchanges between the parental chromosomes, the synaptonemal complex, also promotes exchanges between the sister chromatids. In both cases, exchanges depend on recruitment of the same set of pro-exchange factors to repair sites. Surprisingly, while the synaptonemal complex usually assembles between the two DNA molecules undergoing an exchange, its activity does not rely on a specific chromosome conformation and it can also promote sister exchanges when assembling next to the sisters. This suggests that the synaptonemal complex regulates exchanges by establishing a nuclear domain conducive to nearby coalescence of exchange-promoting factors.

cell biology↗

bioRxiv2021

Heterologous synapsis in C. elegans is regulated by meiotic double-strand breaks and crossovers

Alignment of the parental chromosomes during meiotic prophase is key to the formation of genetic exchanges, or crossovers, and consequently to the successful production of gametes. In almost all studied organisms, alignment involves synapsis: the assembly of a conserved inter-chromosomal interface called the synaptonemal complex (SC). While the SC usually synapses homologous sequences, it can assemble between heterologous sequences. However, little is known about the regulation of heterologous synapsis. Here we study the dynamics of heterologous synapsis in the nematode C. elegans. We characterize two experimental scenarios: SC assembly onto a folded-back chromosome that cannot pair with its homologous partner; and synapsis of pseudo-homologs, a fusion chromosome partnering with an unfused chromosome half its size. We observed elevated levels of heterologous synapsis when the number of meiotic double-strand breaks or crossovers were reduced, indicating that the promiscuity of synapsis is regulated by break formation or repair. By manipulating the levels of breaks and crossovers, we infer both chromosome-specific and nucleus-wide regulation on heterologous synapsis. Finally, we identify differences between the two conditions, suggesting that attachment to the nuclear envelope plays a role in regulating heterologous synapsis.

cell biology↗

bioRxiv2020

Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis

During sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes. This phase-separated interface brings chromosomes together and regulates exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper in C. elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose that the SC brings homologous chromosomes together through two biophysical activities: obligate dimerization that prevents assembly on unpaired chromosomes; and a tendency to phase-separate that extends pairing interactions along the entire length of the chromosomes.

cell biology↗

bioRxiv2020

Meiotic sister chromatid exchanges are rare in C. elegans

Sexual reproduction shuffles the parental genomes to generate new genetic combinations. To achieve that, the genome is subjected to numerous double-strand breaks, the repair of which involves two crucial decisions: repair pathway and repair template. Use of crossover pathways with the homologous chromosome as template exchanges genetic information and directs chromosome segregation. Crossover repair, however, can compromise the integrity of the repair template and is therefore tightly regulated. The extent to which crossover pathways are used during sister-directed repair is unclear, because the identical sister chromatids are difficult to distinguish. Nonetheless, indirect assays have led to the suggestion that inter-sister crossovers, or sister chromatid exchanges (SCEs), are quite common. Here we devised a technique to directly score physiological SCEs in the C. elegans germline using selective sister chromatid labeling with the thymidine analog 5-ethynyl-2-deoxyuridine (EdU). Surprisingly, we find SCEs to be rare in meiosis, accounting for <2% of repair events. SCEs remain rare even when the homologous chromosome is unavailable, indicating that almost all sister-directed repair is channeled into noncrossover pathways. We identify two mechanisms that limit SCEs. First, sister-directed repair intermediates are efficiently inhibited by the RecQ helicase BLMHIM-6. Second, the Synaptonemal Complex-a conserved interface that promotes crossover repair- localizes between the homologous chromosomes and not the sister chromatids. Our data suggest that in C. elegans crossover pathways are only used to generate the single necessary link between the homologous chromosomes. Almost all other breaks, regardless of which repair template they use, are repaired by noncrossover pathways.

cell biology↗

bioRxiv2017

Functional Genes That Distinguish Maize Phyllosphere Metagenomes in Drought and Well-Watered Conditions

The phyllosphere epiphytic microbiome is composed of microorganisms that colonize the external aerial portions of plants. Relationships of plant responses to specific microorganisms-both pathogenic and beneficial-have been examined, but the phyllosphere microbiome functional and metabolic profile responses are not well described. Changing crop growth conditions, such as increased drought, can have profound impacts on crop productivity. Also, epiphytic microbial communities provide a new target for crop yield optimization. We compared Zea mays leaf microbiomes collected under drought and well-watered conditions by examining functional gene annotation patterns across three physically disparate locations each with and without drought treatment, through the application of short read metagenomic sequencing. Drought samples exhibited different functional sequence compositions at each of the three field sites. Maize phyllosphere functional profiles revealed a wide variety of metabolic and regulatory processes that differed in drought and normal water conditions and provide key baseline information for future selective breeding.

microbiology↗