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Disruption of this interaction prevents the activation of the nascent p53. The link of the MDM2 protein\u2014\n                      <jats:italic>p53<\/jats:italic>\n                      mRNA interaction with the upstream DNA damage sensor ATM kinase and the role of the\n                      <jats:italic>p53 mRNA<\/jats:italic>\n                      in the DNA damage sensing mechanism, are still highly anticipated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The proximity ligation assay (PLA) has been extensively used to reveal the sub-cellular localisation of the protein\u2014mRNA and protein\u2013protein interactions. ELISA and co-immunoprecipitation confirmed the interactions in vitro and in cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This study provides a novel mechanism whereby the\n                      <jats:italic>p53 mRNA<\/jats:italic>\n                      interacts with the ATM kinase enzyme and shows that the L22L synonymous mutant, known to alter the secondary structure of the\n                      <jats:italic>p53<\/jats:italic>\n                      mRNA, prevents the interaction. The relevant mechanistic roles in the DNA Damage Sensing pathway, which is linked to downstream DNA damage response, are explored. Following DNA damage (double-stranded DNA breaks activating ATM), activated MDMX protein competes the ATM\u2014\n                      <jats:italic>p53 mRNA<\/jats:italic>\n                      interaction and prevents the association of the\n                      <jats:italic>p53 mRNA<\/jats:italic>\n                      with NBS1 (MRN complex). These data also reveal the binding domains and the phosphorylation events on ATM that regulate the interaction and the trafficking of the complex to the cytoplasm.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The presented model shows a novel interaction of ATM with the\n                      <jats:italic>p53<\/jats:italic>\n                      mRNA and describes the link between DNA Damage Sensing with the downstream p53 activation pathways; supporting the rising functional implications of synonymous mutations altering secondary mRNA structures.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12943-024-01933-z","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T02:02:36Z","timestamp":1705975356000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["The DNA damage sensor ATM kinase interacts with the p53 mRNA and guides the DNA damage response pathway"],"prefix":"10.1186","volume":"23","author":[{"given":"Konstantinos","family":"Karakostis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Malbert-Colas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Thermou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borek","family":"Vojtesek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"F\u00e5hraeus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"1933_CR1","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12943-019-1100-5","volume":"18","author":"L Bian","year":"2019","unstructured":"Bian L, Meng Y, Zhang M, Li D. MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment. Mol Cancer. 2019;18:169.","journal-title":"Mol Cancer"},{"key":"1933_CR2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3389\/fgene.2013.00037","volume":"4","author":"TH Stracker","year":"2013","unstructured":"Stracker TH, Roig I, Knobel PA, Marjanovic M. The ATM signaling network in development and disease. Front Genet. 2013;4:37.","journal-title":"Front Genet"},{"key":"1933_CR3","doi-asserted-by":"publisher","first-page":"472","DOI":"10.4161\/cc.9.3.10556","volume":"9","author":"Q Cheng","year":"2010","unstructured":"Cheng Q, Chen J. Mechanism of p53 stabilization by ATM after DNA damage. 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