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N-hydroxy-pipecolic acid (NHP) is a mobile signal required to initiate and amplify SAR signaling in different plant species. However, the key regulators involved in activating NHP-mediated signaling and systemic resistance remain unclear. In this study, we identified an Arabidopsis (Arabidopsis thaliana) mutant, dawdle (ddl), that exhibits a compromised systemic resistance phenotype upon NHP treatment and pathogen infection. Transcriptome profiling revealed that the DDL mutation significantly reduces the expression of NHP-responsive genes in both local treated and distal untreated leaves. Many of these NHP-responsive genes are associated with PAMP-triggered immunity, salicylic acid (SA) and NHP metabolism, SA signaling, and SAR, indicating that DDL is required for an effective NHP response and the activation of systemic transcriptional reprogramming. In addition to mediating NHP-mediated signal transduction, DDL is critical for enhancing PR1 gene expression during the pathogen challenge. Metabolite profiling indicated that the DDL mutation reduces free SA levels in Pst-inoculated tissues while enhancing NHP and SA accumulation in distal, untreated leaves, suggesting that DDL may regulate both biosynthesis and homeostasis of these metabolites. Moreover, loss of DDL decreases plant sensitivity to exogenous NHP, but not to SA, indicating that DDL may specifically regulate NHP perception or signal transduction. Our findings suggest that DDL plays a role in NHP-mediated systemic transcriptional reprogramming and systemic resistance, as well as in gene expression regulation during secondary pathogen challenge.<\/jats:p>","DOI":"10.1093\/plphys\/kiaf536","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:29:59Z","timestamp":1761222599000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>N<\/i>\n                    -hydroxy-pipecolic acid-mediated signal transduction and resistance requires\n                    <i>DAWDLE<\/i>"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5991-2991","authenticated-orcid":false,"given":"Jung-Kai","family":"Hsu","sequence":"first","affiliation":[{"name":"Biotechnology Center in Southern Taiwan, Academia Sinica , Tainan 711 ,","place":["Taiwan"]},{"name":"Agricultural Biotechnology Research Center, Academia Sinica , Taipei 115 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115 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5017-0911","authenticated-orcid":false,"given":"Sy-Chyi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Biotechnology Center in Southern Taiwan, Academia Sinica , Tainan 711 ,","place":["Taiwan"]},{"name":"Agricultural Biotechnology Research Center, Academia Sinica , Taipei 115 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9390-795X","authenticated-orcid":false,"given":"Yao-Cheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Biotechnology Center in Southern Taiwan, Academia Sinica , Tainan 711 ,","place":["Taiwan"]},{"name":"Agricultural Biotechnology Research Center, Academia Sinica , Taipei 115 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