{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:12:57Z","timestamp":1768623177939,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["#1104186"],"award-info":[{"award-number":["#1104186"]}]},{"name":"Mater Foundation Smiling","award":["#1104186"],"award-info":[{"award-number":["#1104186"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An apical component of the cell cycle checkpoint and DNA damage repair response is the ataxia-telangiectasia mutated (ATM) Ser\/Thr protein kinase. A variant of ATM, Ser49Cys (rs1800054; minor allele frequency = 0.011), has been associated with an elevated risk of melanoma development; however, the functional consequence of this variant is not defined. ATM-dependent signalling in response to DNA damage has been assessed in a panel of patient-derived lymphoblastoid lines and primary human melanocytic cell strains heterozygous for the ATM Ser49Cys variant allele. The ATM Ser49Cys allele appears functional for acute p53-dependent signalling in response to DNA damage. Expression of the variant allele did reduce the efficacy of oncogene expression in inducing senescence. These findings demonstrate that the ATM 146C&gt;G Ser49Cys allele has little discernible effect on the acute response to DNA damage but has reduced function observed in the chronic response to oncogene over-expression. Analysis of melanoma, naevus and skin colour genomics and GWAS analyses have demonstrated no association of this variant with any of these outcomes. The modest loss of function detected suggest that the variant may act as a modifier of other variants of ATM\/p53-dependent signalling.<\/jats:p>","DOI":"10.3390\/ijms25031664","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T12:25:01Z","timestamp":1706531101000},"page":"1664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The ATM Ser49Cys Variant Effects ATM Function as a Regulator of Oncogene-Induced Senescence"],"prefix":"10.3390","volume":"25","author":[{"given":"Caroline","family":"Atkinson","sequence":"first","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aideen M.","family":"McInerney-Leo","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Proctor","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Lanagan","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander J.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6485-9952","authenticated-orcid":false,"given":"Farhad","family":"Dehkhoda","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Caole","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1035-7279","authenticated-orcid":false,"given":"Ellie","family":"Maas","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Ainger","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia L.","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Queensland Institute for Medical Research Berghofer, Brisbane, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Johansson","sequence":"additional","affiliation":[{"name":"Queensland Institute for Medical Research Berghofer, Brisbane, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Leo","sequence":"additional","affiliation":[{"name":"Centre of Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD 4059, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas K.","family":"Hayward","sequence":"additional","affiliation":[{"name":"Queensland Institute for Medical Research Berghofer, Brisbane, QLD 4006, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Sturm","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma L.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Twin Research and Genetic Epidemiology, School of Life Course & Population Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3933-1651","authenticated-orcid":false,"given":"Brian","family":"Gabrielli","sequence":"additional","affiliation":[{"name":"Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature01368","article-title":"DNA damage activates ATM through intermolecular autophosphorylation and dimer 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