{"id":49753,"date":"2017-07-27T00:00:00","date_gmt":"2017-07-26T23:00:00","guid":{"rendered":"http:\/\/www.pcb.ub.edu\/errors-made-by-dna-spellchecker-revealed-as-important-cause-of-cancer\/"},"modified":"2020-11-18T14:59:06","modified_gmt":"2020-11-18T13:59:06","slug":"errors-made-by-dna-spellchecker-revealed-as-important-cause-of-cancer","status":"publish","type":"post","link":"https:\/\/www.pcb.ub.edu\/en\/errors-made-by-dna-spellchecker-revealed-as-important-cause-of-cancer\/","title":{"rendered":"Errors made by &#8216;DNA spellchecker\u2019 revealed as important cause of cancer"},"content":{"rendered":"<p>Cancer is mostly caused by changes in the DNA of our cells that occur during our lifetime rather than those that we inherit from our parents. Identifying the causes of these \u2018mutations\u2019 is a difficult challenge because many processes can result in an identical DNA sequence change in a genome. A study developed by <a href=\"https:\/\/www.irbbarcelona.org\/en\/profile\/fran-supek\" target=\"_blank\" rel=\"noopener noreferrer\">Fran Supek <\/a>and\u00a0<a href=\"http:\/\/www.crg.eu\/ben_lehner\" target=\"_blank\" rel=\"noopener noreferrer\">Ben Lehner<\/a>\u00a0have now\u00a0identified one of the important mechanisms that causes these mutations as mistakes made by a DNA \u2018spellchecker\u2019 that repairs damage in our genomes.<\/p>\n<p>The researchers identified this process by\u00a0studying clusters of mutations in more than a thousand tumor genomes, meaning that they hunted for mutations that occur close together in the same part of the genome, such that this is highly unlikely to have happened by chance. The goal was to get a better picture of the\u00a0mutagenic factors that affect human cells and that might cause cancer.<\/p>\n<p>\u00a0\u201cClustered mutations are likely to be generated at the same moment in time, so\u00a0by looking at several neighboring mutations at once, we can have a better understanding of what has damaged the DNA,\u201d\u00a0says\u00a0Fran Supek,\u00a0first author of the study and currently group leader and \u2018Ramon y Cajal\u2019 fellow at IRB Barcelona.\u00a0\u201cLike when police study a pattern of recurrent crimes in order to find a serial killer,\u00a0here\u00a0we show that focusing on patterns of clustered mutations and using a large number of cancer genomes, we can identify the culprits that cause mutations in tumors,\u201d\u00a0he explains.<\/p>\n<p>\n<span style=\"font-size:16px\"><strong>New evidence links high levels of alcohol, sunlight, and smoking to mutations<\/strong><\/span><\/p>\n<p>By studying clusters, the scientists identified\u00a0nine mutational signatures that were evident in more than 1,000 genomes of tumors from various organs. Their results,\u00a0\u00a0ublished in\u00a0Cell\u00a0on 27th\u00a0July, revealed new major mutation-causing processes, including an unusual case of DNA repair which should normally safeguard the genome from damage, but is sometimes subverted and starts introducing clustered mutations.<\/p>\n<p>DNA repair is extremely important because our bodies are constantly renewing their cells which involves copying more than 2 meters of DNA and errors inevitably get introduced. Moreover,\u00a0mutagens in the environment like sunlight and tobacco smoke damage DNA and this damage has to be corrected.\u00a0 DNA repair is normally exquisitely accurate, but some types of damage can only be corrected using lower-fidelity \u2018spellcheckers\u2019. It is the mistakes made by one of these less accurate spellcheckers that cause many of the mutations seen in different types of tumors, including liver, colon, stomach, esophagus and lung cancer.\u00a0<\/p>\n<p>Alcohol is a well-known contributor to many types of cancer, but the reasons for this are surprisingly unclear. Supek and Lehner\u2019s work suggests that one effect of alcohol, when consumed in large amounts, is to increase the use of low-fidelity DNA repair, thereby increasing the mutation rate in the most important regions of the genome. This finding provides a first glimpse into one mechanism by which alcohol may contribute to cancer risk. \u00a0\u00a0High exposure to sunlight seems to have a similar consequence.<\/p>\n<p>As another part of the study scientists also found that cigarette smoking is associated with several different kinds of clustered mutations, further revealing the details of how smoking results in horrific damage to our DNA.<br \/>\n\u00a0<\/p>\n<p><strong>\u25ba More information:<\/strong>\u00a0Web de l<strong>&#8216;<a href=\"https:\/\/www.irbbarcelona.org\/ca\/news\/els-errors-introduits-pel-corrector-de-ladn-son-una-important-causa-de-cancer\" target=\"_blank\" rel=\"noopener noreferrer\">IRB Barcelona [+]<\/a><\/strong><\/p>\n<p><strong>\u25ba Reference article:\u00a0<\/strong><br \/>\nSupek, Fran and Lehner, Ben. &#8220;<a href=\"http:\/\/www.cell.com\/cell\/abstract\/S0092-8674(17)30774-2\" target=\"_blank\" rel=\"noopener noreferrer\">Clustered mutation signatures reveal that error-prone DNA repair targets mutations to active genes<\/a>&#8220;.\u00a0Cell. 27 (2017). DOI:\u00a010.1016\/j.cell.2017.07.003<\/p>\n<p style=\"font-family: heuristicaregular, arial, sans-serif;font-size: 15px\">\u00a0<\/p>\n<p style=\"font-family: heuristicaregular, arial, sans-serif;font-size: 15px\">\u00a0<\/p>\n<p style=\"font-family: heuristicaregular, arial, sans-serif;font-size: 15px\">\u00a0<\/p>\n<p style=\"font-family: heuristicaregular, arial, sans-serif;font-size: 15px\">\u00a0<\/p>\n<p>\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A study developed by Fran Supek (currently a group leader at <a href=\"http:\/\/www.pcb.ub.edu\/portal\/en\/cerca?p_p_id=cercador_WAR_empleatsempresesportlet&amp;p_p_lifecycle=0&amp;p_p_state=maximized&amp;p_p_mode=view&amp;p_p_col_id=column-1&amp;p_p_col_count=1&amp;_cercador_WAR_empleatsempresesportlet_jspPage=%2Fhtml%2Fcommon%2Fdetall-empresa.jsp&amp;_cercador_WAR_empleatsempresesportlet_empresaId=ENT_000001&amp;_cercador_WAR_empleatsempresesportlet_redirect=%2Fportal%2Fca%2Fcerca%3Fp_p_id%3Dcercador_WAR_empleatsempresesportlet%26p_p_lifecycle%3D0%26p_p_mode%3Dview%26_cercador_WAR_empleatsempresesportlet_keywords%3Dirb%26_cercador_WAR_empleatsempresesportlet_tab%3D1\" target=\"_blank\" rel=\"noopener noreferrer\">IRB Barcelona<\/a> at the Barcelona Science\u00a0Park) and\u00a0Ben Lehner\u00a0at the Centre for Genomic Regulation (<a href=\"http:\/\/www.crg.eu\/en\" target=\"_blank\" rel=\"noopener noreferrer\">CRG<\/a>) in Barcelona reveal that many mutations in human cancers are caused by mistakes made by a repair mechanism or \u2018DNA spellchecker\u2019 rather than the actual damage to DNA caused by the environment.\u00a0High levels of alcohol, sunlight, and tobacco consumption increase the rate at which this happens, resulting in more mutations in the most important parts of our genomes.<\/p>\n<p>\u00a0<\/p>\n","protected":false},"author":1,"featured_media":54101,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[8],"tags":[],"class_list":["post-49753","post","type-post","status-publish","format-standard","has-post-thumbnail","category-uncategorized"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.7 - 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