{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:19:09Z","timestamp":1790677149200,"version":"4.1.0"},"reference-count":44,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T00:00:00Z","timestamp":1533859200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002878","name":"Consejer\u00eda de Econom\u00eda, Innovaci\u00f3n, Ciencia y Empleo, Junta de Andaluc\u00eda","doi-asserted-by":"publisher","award":["P09CT54967"],"award-info":[{"award-number":["P09CT54967"]}],"id":[{"id":"10.13039\/501100002878","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Juan de la cierva grant from Ministry of Economy, Industry and Competitiveness, Government of Spain","award":["IJCI-2014-22549"],"award-info":[{"award-number":["IJCI-2014-22549"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Photoreceptors, light-sensing neurons in retina, are central to vision. Photoreceptor cell death (PCD) is observed in most inherited and acquired retinal dystrophies. But the underlying molecular mechanism of PCD is unclear. Photoreceptors are sturdy neurons that survive high oxidative and phototoxic stress, which are known threats to genome stability. Unexpectedly, DNA damage response in mice photoreceptors is compromised; mainly due to loss of crucial DNA repair proteins, ATM and 53BP1. We tried to understand the molecular function of ATM and 53BP1 in response to oxidative stress and how suppression of DNA repair response in mice retina affect photoreceptor cell survival.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    We use the state of art cell biology methods and structure-function analysis of mice retina. RNA:DNA hybrids (S9.6 antibody and Hybrid-binding domain of RNaseH1) and DNA repair foci (gH2AX and 53BP1) are quantified by confocal microscopy, in retinal sections and cultured cell lines. Oxidative stress, DNA double strand break, RNaseH1 expression and small-molecule kinase-inhibitors were used to understand the role of ATM and RNA:DNA hybrids in DNA repair. Lastly, retinal structure and function of ATM deficient mice, in Retinal degeneration 1 (Pde6brd1) background, is studied using Immunohistochemistry and Electroretinography.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    Our work has three novel findings: firstly, both human and mice photoreceptor cells specifically accumulate RNA:DNA hybrids, a structure formed by re-hybridization of nascent RNA with template DNA during transcription. Secondly, RNA:DNA-hybrids promote ataxia-telangiectasia mutated (ATM) activation during oxidative stress and 53BP1-foci formation during downstream DNA repair process. Thirdly, loss of ATM -in murine photoreceptors- protract DNA repair but also promote their survival.\u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    We propose that due to high oxidative stress and accumulation of RNA:DNA-hybrids in photoreceptors, expression of ATM is tightly regulated to prevent PCD. Inefficient regulation of ATM expression could be central to PCD and inhibition of ATM-activation could suppress PCD in retinal dystrophy patients.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.15579.1","type":"journal-article","created":{"date-parts":[[2018,8,10]],"date-time":"2018-08-10T05:00:07Z","timestamp":1533877207000},"page":"1233","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Formation of 53BP1 foci and ATM activation under oxidative stress is facilitated by RNA:DNA hybrids and loss of ATM-53BP1 expression promotes photoreceptor cell survival in mice"],"prefix":"10.12688","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4553-7824","authenticated-orcid":false,"given":"Vaibhav","family":"Bhatia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Vald\u00e9s-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-4574","authenticated-orcid":false,"given":"Daniel","family":"Rodriguez-Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shom Shankar","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2018,8,10]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"273-84","DOI":"10.1038\/nrg2717","article-title":"Photoreceptor degeneration: genetic and 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.16994.r37370, Travis H. Stracker, Institute for Research in Biomedicine (IRB Barcelona) and the Barcelona Institute of Science and Technology, Barcelona, Spain, 30 Aug 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1233\/v1#referee-response-37370","order":0,"name":"referee-response-37370","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.16994.r37369, Hemant Khanna, Department of Ophthalmology and Visual Sciences, University of Massachusetts Medical School (UMMS), Worcester, MA, USA, 04 Sep 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1233\/v1#referee-response-37369","order":1,"name":"referee-response-37369","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.16994.r38310, Florian Frohns, Radiation Biology and DNA Repair, Darmstadt University of Technology, Darmstadt, Germany, 27 Sep 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1233\/v1#referee-response-38310","order":2,"name":"referee-response-38310","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.16994.r38194, Maria Tresini, \u00a0Department of Molecular Genetics, Erasmus University Medical Center\u00a0(Erasmus MC), Rotterdam, The Netherlands, 05 Nov 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1233\/v1#referee-response-38194","order":3,"name":"referee-response-38194","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>vaibhav bhatia<\/b>; \n<i>Posted: 28 Sep 2018<\/i>; Dear Travis, Hemant and Florian,  I want to thank all of you for the time and efforts spent to review our manuscript. All the authors of this paper are very grateful to have received such insightful comments from very observant scientists in the field. This certainly will help us to improve our manuscript. We have already started working on the second version of the paper. I will upload it on f1000-portal before the end of October and hope to address the concerns of all three reviewers.&nbsp;  Thanking you again  Kind regards Vaibhav Bhatia","URL":"https:\/\/f1000research.com\/articles\/7-1233\/v1#article-response-4019","order":4,"name":"article-response-4019","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"The work is supported by Junta de Andalucia, Spain (P09CT54967) and Juan de la Cierva grants (IJCI-2014-22549) from the Ministry of Economy, Industry and Competitiveness, Government of Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}