LAUSR

As global climate change threatens food security, heat tolerance in plants has become a central topic for researchers. It is known that rising temperatures affect crop growth and yield in multiple ways. However, a topic of essential importance, yet widely uncharted, is the maintenance of genome integrity after heat-stress-induced DNA damage1. In this issue of Nature Plants, Han et al.2 unveiled a surprising and direct link between the transcriptional control of DNA repair genes and thermotolerance in plants. Already more than ten years ago, in a groundbreaking study, it was shown that the expression of DNA repair genes is upregulated by the plant-specific transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1) in the presence of DNA damage3. Now, the current study has demonstrated that there is crosstalk between heat stress and genotoxic stress in Arabidopsis. In eukaryotes, central players for maintaining genome stability are RECQ helicases4. Although they are present as a multigene family in plant genomes5, so far only RECQ4 homologues have been functionally well-characterized in vivo and demonstrated to be involved in DNA repair in somatic cells6 as well as in crossover control in meiosis7. The AtRECQ2 helicase is homologous to the Werner protein, which has been shown to result in a severe genetic disease in humans when mutated. Although biochemical studies have demonstrated early on that its open reading frame codes for an active DNA helicase8,9, surprisingly, no defect in DNA repair could be revealed by mutant analysis, until now10. The study of Han et al. has solved this mystery by demonstrating that RECQ2 does indeed have an important function in DNA repair in vivo; however, this function operates exclusively under heat stress. The starting point of the study from Han et al. was the analysis of a distinct thermosensitive phenotype of Arabidopsis mutants lacking the RING finger-containing E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1). These mutants depicted a lower survival rate than wild-type plants after heat treatment at 37 °C, and the increased leakage of electrolytes hinted to drastic cell damage. However, so far characterized roles of HOS1 as a ubiquitin ligase and suppressor of thermomorphogenesis via PHYTOCHROME INTERACTING FACTOR 4 (PIF4) suppression did not turn out to play a role in this heat stress endurance. Therefore, the authors performed a RNA sequencing analysis to elucidate how HOS1 might convey thermotolerance. By comparing the global expression levels of wild-type and hos1 mutant plants grown under normal and high temperatures, they were able to not only define differences in global gene expression profiles but also to identify genes specifically regulated by HOS1 under heat stress. Surprisingly, a large number of DNA damage response genes did not show transcriptional upregulation in hos1 mutants in response to high temperatures. And indeed, this astonishing link could be confirmed using the comet assay: DNA damage was shown to accumulate in the hos1 mutants. These findings opened the door for a more detailed analysis of DNA repair under heat stress. The RECQ helicase RECQ2 came into focus in the study, as the recq2 mutant depicted the highest reduction of thermotolerance of all tested mutants of DNA repair factors regulated by HOS1. In this mutant, an increased amount of DNA breaks at high temperatures was detected. Moreover, the involvement of HOS1 and RECQ2 in a common, so far unrevealed, repair pathway for heat-induced DNA damage could be demonstrated by the enhanced sensitivity of both mutants towards DNA crosslinking agents exclusively at high temperatures. Thus, for the first time a specific temperature-dependent DNA damage response could be documented in plants. However, the central question of how heat stress signals are integrated into the transcriptional control of DNA repair genes by HOS1 remained. Therefore, the authors measured protein levels of HOS1 before and after heat exposure. Interestingly, the protein amount increased fivefold after heat exposure. This effect could be imitated at lower temperatures through the application of a proteasome inhibitor, resulting in a threefold induction. Apparently, HOS1 gets degraded by the proteasome at low temperatures, which is inhibited when the temperature rises, leading to a temperature-dependent activation of HOS1. HSFA1s