Biology subjects

Jessop, A.

Publications and source records attributed to Jessop, A..

3 recordsLinked to original sources

bioRxiv2025

Structural basis for Rad54- and Hed1-mediated regulation of Rad51 during the transition from mitotic to meiotic recombination

Rad51 catalyzes the DNA pairing reactions that take place during homologous recombination (HR), and HR must be tightly regulated to ensure physiologically appropriate outcomes. Rad54 is an ATP-dependent DNA motor protein that stimulates Rad51 activity during mitosis. In meiosis Rad51 is downregulated by the protein Hed1, which blocks Rad54 binding to Rad51, and allows Dmc1 to function as the active recombinase. We currently have a poor understanding of the regulatory interplay between Rad54, Hed1, Rad51 and Dmc1. Here, we identify a conserved Rad51 interaction motif within Rad54, and we solve a CryoEM structure of this motif bound to Rad51. We also identify a distinct Rad51 interaction motif within Hed1 and solve its structure bound to Rad51. These structures explain how Rad54 engages Rad51 to promote recombination between sister chromatids during mitosis and how Rad51 is downregulated by Hed1 upon entry into meiosis such that its meiosis-specific homolog Dmc1 can promote recombination between homologous chromosomes.

biochemistry↗

bioRxiv2024

Lineage-specific amino acids define functional attributes of the protomer-protomer interfaces for the Rad51 and Dmc1 recombinases

Most eukaryotes possess two Rad51/RecA family DNA recombinases that are thought to have arisen from an ancient gene duplication event: Rad51, which is expressed in both mitosis and meiosis; and Dmc1, which is only expressed in meiosis. To explore the evolutionary relationship between these recombinases, here, we present high-resolution CryoEM structures of S. cerevisiae Rad51 filaments and S. cerevisiae Dmc1 filaments bound to ssDNA, which reveal a pair of stacked interfacial aromatic amino acid residues that are nearly universally conserved in Rad51 but are absent from Dmc1. We use a combination of bioinformatics, genetic analysis of natural sequence variation, and deep mutational analysis to probe the functionally tolerated sequence space for these stacked aromatic residues. Our findings demonstrate that the functional landscape of the interfacial aromatic residues within the Rad51 filament is highly constrained. In contrast, the amino acids at the equivalent positions within the Dmc1 filament exhibit a broad functional landscape. This work helps highlight the distinct evolutionary trajectories of these two eukaryotic recombinases, which may have contributed to their functional and mechanistic divergence. AUTHOR SUMMARYMost eukaryotic organisms have two closely related proteins, Rad51 and Dmc1, that are needed for different aspects of genetic recombination. These proteins may have evolved from a single gene that was duplicated during the early evolution of eukaryotes. Rad51 is active during both normal cell division (mitosis) and sexual reproduction (meiosis), while Dmc1 is only active during meiosis. To better understand how these proteins are related, we studied their three-dimensional structures using high resolution cryogenic electron microscopy. Our findings show that Rad51 has a specific set of conserved amino acids located at the protein interfaces, but this set of amino acids is different in Dmc1. We used a series of genetic approaches to analyze how these amino acids affect the proteins function. Our results show that Rad51 has a strict set of rules governing the identify of these amino acids, whereas Dmc1 does not. This research sheds light on how Rad51 and Dmc1 have evolved differently, leading to distinct functions in genetic recombination.

genetics↗

bioRxiv2023

Invasive traits of freshwater fish database (ITOFF)

AIMSpecies invasions are a major driver of global biodiversity loss, but only a minority of invasions are successful. Evidence suggests that invasive success is linked to life-history traits. Yet, data on invasive success and species traits remain fragmented across multiple sources. Here we present the Invasive Traits of Freshwater Fish (ITOFF) database, an interdisciplinary framework that integrates multiple datasets to elucidate the role of life-history traits in shaping invasive success. ITOFF allows seamless access to invasive species data and fosters collaborative actions through knowledge sharing. ITOFF is supported by an innovative web-application that makes complex relationships between invasive and native species accessible to a broad audience. The scientific contribution of ITOFF is illustrated by examining the role of life-history traits and phylogeny in invasion success. LOCATIONGlobal. METHODSGeneralized linear models were used to test the contribution of generation time, trophic level, longevity, and temperature range to invasive success. Through divisive cluster analysis we investigate the role of multiple traits in determining invasive success. Finally, we construct phylogenetic trees to investigate the role of evolutionary history in the invasion process. RESULTSITOFF unifies data for 1917 freshwater fish species representative of invasive species, those species they endanger, and species impacted by invasives but not considered endangered. Invasive species are generally characterized by greater temperature ranges, but are indistinguishable from impacted, endangered, and critically endangered species for the remaining life-history traits. Further, we show that invasive species are generally not distinct from impacted or endangered species when considering multiple traits or phylogeny. MAIN CONCLUSIONSITOFF provides an accessible platform for the improved forecasting of species invasions. ITOFF data shows that classical predictions of life-history traits determining invasive success do not hold amongst freshwater fish species. Forecasting of invasive species must therefore shift towards a wholistic approach encompassing the species and the environment.

ecology↗