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Biology subjects

Campbell, D. M.

Publications and source records attributed to Campbell, D. M..

2 recordsLinked to original sources

A specialized SUV3 RNA helicase is involved in plant mitochondrial DNA repair

Synonymous substitution rates in the coding regions of land plant mitochondrial genomes are substantially lower than those in the nucleus. In contrast, non-coding regions are difficult or impossible to align except among very closely related species, suggesting that point mutation rates in these regions are considerably higher. Rearrangement breakpoints occur frequently within non-coding DNA, generating duplications, deletions, and inversions. To reconcile these contradictory patterns of genome evolution, it has been proposed that DNA damage is converted into double-strand breaks that are repaired through a combination of template-directed mechanisms and non-homologous end joining, while purifying selection preserves the integrity of coding sequences. Here we characterized AtSUV3, a mitochondrially targeted RNA helicase encoded by Arabidopsis thaliana At4g14790, a gene previously proposed to function as part of the plant mitochondrial degradosome. Mutations in AtSUV3 confer hypersensitivity to ciprofloxacin-induced mitochondrial DNA damage, CRISPR- knockout lines display increased ectopic recombination in the mitochondrial genome, and recombinant AtSUV3 exhibits ATP-dependent RNA helicase activity with a preference for 3'-ended substrates. Together, these findings identify AtSUV3 as a factor involved in mitochondrial dsDNA break repair. Consistent with our results, Arabidopsis and other plants encode an uncharacterized gene, AT5G39840.1, with 75% amino acid similarity with AtSUV3, dubbed herein as SUV3-like. We hypothesize that the AtSUV3 paralog has undergone specialization towards DNA repair, whereas AtSUV3-like protein may play a role in the plant organellar degradosome. Collectively, these findings identify AtSUV3 as a previously unrecognized factor involved in mitochondrial dsDNA break repair and provide a framework for understanding the diversification of DNA repair proteins during plant evolution.

plant biology↗

Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms

Most human Transcription factors (TFs) genes encode multiple protein isoforms differing in DNA binding domains, effector domains, or other protein regions. The global extent to which this results in functional differences between isoforms remains unknown. Here, we systematically compared 693 isoforms of 246 TF genes, assessing DNA binding, protein binding, transcriptional activation, subcellular localization, and condensate formation. Relative to reference isoforms, two-thirds of alternative TF isoforms exhibit differences in one or more molecular activities, which often could not be predicted from sequence. We observed two primary categories of alternative TF isoforms: "rewirers" and "negative regulators", both of which were associated with differentiation and cancer. Our results support a model wherein the relative expression levels of, and interactions involving, TF isoforms add an understudied layer of complexity to gene regulatory networks, demonstrating the importance of isoform-aware characterization of TF functions and providing a rich resource for further studies.

systems biology↗