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It has clear roles in controlling cell cycle, triggering apoptosis, activating autophagy and modulating DNA damage response. Little is known about the role of p53 in autophagy\u2010associated cell death, which can be induced by photoactivation of photosensitizers within cells. The photosensitizer 1,9\u2010dimethyl methylene blue (DMMB) within nanomolar concentration regimes has specific intracellular targets (mitochondria and lysosomes), photoinducing a typical scenario of cell death with autophagy. Importantly, in consequence of its subcellular localization, photoactive DMMB induces selective damage to mitochondrial DNA, saving nuclear DNA. By challenging cells having different p53 protein levels, we investigated whether p53 modulates DMMB\/light\u2010induced phototoxicity and cell cycle dynamics. Cells lacking p53 activity were slightly more resistant to photoactivated DMMB, which was correlated with a smaller sub\u2010G1 population, indicative of a lower level of apoptosis. DMMB photosensitization seems to induce mostly autophagy\u2010associated cell death and S\u2010phase cell cycle arrest with replication stress. Remarkably, these responses were independent on the p53 status, indicating that p53 is not involved in either process. Despite describing some p53\u2010related responses in cells challenged by photosensitization, our results also provide novel information on the consequences of DMMB phototoxicity.<\/jats:p>","DOI":"10.1111\/php.13019","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T02:19:05Z","timestamp":1537582745000},"page":"355-363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["p53\u2010Dependent and p53\u2010Independent Responses of Cells Challenged by Photosensitization"],"prefix":"10.1111","volume":"95","author":[{"given":"Aline B. de P.","family":"Abrantes","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Qu\u00edmica Universidade de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo C.","family":"Dias","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Qu\u00edmica Universidade de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja C.","family":"Souza\u2010Pinto","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Qu\u00edmica Universidade de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio S.","family":"Baptista","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Qu\u00edmica Universidade de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3711"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7973635"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.212282.112"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1730"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026120"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2529"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160920523"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06788-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20114"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1078960"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3179-7"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1515609"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1572-1000(05)00007-4"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.07.012"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5PP00251F"},{"key":"e_1_2_7_17_1","first-page":"331","article-title":"Photodynamic therapy sensitivity is not altered in human tumor cells after abrogation of p53 function","volume":"59","author":"Fisher A.","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0131-3"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.1997.tb08653.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1011-1344(97)00130-9"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(99)00013-0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1562\/0031-8655(2000)0710201TROTPT2.0.CO2"},{"key":"e_1_2_7_23_1","first-page":"951","article-title":"Wild\u2010type p53 gene transfer into mutated p53 HT29 cells improves sensitivity to photodynamic therapy via induction of apoptosis","volume":"24","author":"Barberi\u2010Heyob M.","year":"2004","journal-title":"Int. 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