RESUMO
Homologous recombination (HR) deficiency enhances sensitivity to DNA damaging agents commonly used to treat cancer. In HR-proficient cancers, metabolic mechanisms driving response or resistance to DNA damaging agents remain unclear. Here we identified that depletion of alpha-ketoglutarate (αKG) sensitizes HR-proficient cells to DNA damaging agents by metabolic regulation of histone acetylation. αKG is required for the activity of αKG-dependent dioxygenases (αKGDDs), and prior work has shown that changes in αKGDD affect demethylases. Using a targeted CRISPR knockout library consisting of 64 αKGDDs, we discovered that Trimethyllysine Hydroxylase Epsilon (TMLHE), the first and rate-limiting enzyme in de novo carnitine synthesis, is necessary for proliferation of HR-proficient cells in the presence of DNA damaging agents. Unexpectedly, αKG-mediated TMLHE-dependent carnitine synthesis was required for histone acetylation, while histone methylation was affected but dispensable. The increase in histone acetylation via αKG-dependent carnitine synthesis promoted HR-mediated DNA repair through site- and substrate-specific histone acetylation. These data demonstrate for the first time that HR-proficiency is mediated through αKG directly influencing histone acetylation via carnitine synthesis and provide a metabolic avenue to induce HR-deficiency and sensitivity to DNA damaging agents.
RESUMO
Spotted lanternfly (Lycorma delicatula) is a recently introduced pest in the United States, where it threatens the wine, timber, and ornamentals industries. Knowledge of the dispersal ability of L. delicatula is key to developing effective management strategies for this invasive pest. We conducted a mark, release, re-sight study, marking nymphs with fluorescent powders and observing dispersal distances from a central release point at three time points over 7 d following release. To examine how dispersal patterns changed over the course of nymphal development, we repeated this process for each of L. delicatula's four instars. All releases were conducted in contiguous, deciduous forest, which is a widespread habitat type within L. delicatula's invaded range and a habitat where this pest may have negative ecological and economic impacts. We found that nymphs displayed clear directionality in their movement following release, apparently preferring to move uphill on the modest 6° grade at our release site. Most nymphs remained near the release location, while some moved tens of meters. The maximum displacement we observed was 65 m from the release point, 10 d after release. Nymphs were re-sighted singly and in small groups on a variety of trees, shrubs, and understory vegetation. All four instars had similar dispersal distances over time, though third instar nymphs moved farthest on average, with estimated median displacement of 16.9 m 7 d after release. Further studies are needed to provide additional information on what factors influence spotted lanternfly dispersal.
Assuntos
Hemípteros , Animais , Florestas , Ninfa , ÁrvoresRESUMO
Despite its broad host range, the spotted lanternfly Lycorma delicatula (White), is known to have a marked preference for Ailanthus altissima. However, whether this polyphagous phloem feeder can complete its life cycle in the absence of A. altissima is unknown. We examined the performance of L. delicatula with and without access to A. altissima by tracking development, survival, host tree species association, and oviposition in large enclosures planted with Salix babylonica and Acer saccharinum along with either A. altissima or Betula nigra. We monitored enclosures from late May 2019 through June 2020. Lycorma delicatula survival was slightly higher in enclosures with A. altissima and 50% of individuals in A. altissima enclosures reached the adult stage ~6.5 d earlier than in enclosures without A. altissima. In the presence of A. altissima, nymphs were most frequently observed on this host while adults were found at similar frequencies on A. altissima and A. saccharinum. In the absence of A. altissima, nymphs were most frequently associated with S. babylonica and A. saccharinum, while adults were most often found on A. saccharinum. Females laid a total of 46 and 6 egg masses in enclosures with and without A. altissima, respectively, before freezing temperatures killed the remaining adults. The proportion of eggs that hatched per egg mass did not differ between treatments. Although L. delicatula can complete development and reproduce on other host species without access to A. altissima, fitness was reduced. These findings have implications for management that relies exclusively on treatment of A. altissima.