{"id":4257,"date":"2017-02-07T05:00:00","date_gmt":"2017-02-07T10:00:00","guid":{"rendered":"https:\/\/www.med.unc.edu\/biochem\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/"},"modified":"2018-08-01T10:33:16","modified_gmt":"2018-08-01T14:33:16","slug":"how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/biochem\/news\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/","title":{"rendered":"How Life Survives: UNC researchers confirm basic mechanism of DNA repair"},"content":{"rendered":"<div>\n<p class=\"lead\">Findings come from an advanced DNA sequencing application developed by the lab of University of North Carolina Nobel Laureate Aziz Sancar.<\/p>\n<div class=\"image-section\">\n<figure class=\"thumbnail wp-caption alignright\">\n    <img loading=\"lazy\" decoding=\"async\" class=\"size-medium wp-image-4258\" src=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2018\/07\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair-image2-300x227.jpeg\" width=\"300\" height=\"200\" alt=\"image2\"\/><figcaption class=\"caption wp-caption-text\">Chris Selby, PhD; Aziz Sancar, MD, PhD; and Ogun Adebali, PhD<br \/>\n    <\/figcaption><\/figure>\n<\/div>\n<div>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">Day in and day out, in our bodies, the DNA in cells is damaged for a variety of reasons, and thus intercellular DNA-repair systems are fundamental to the maintenance of life. Now scientists from the UNC School of Medicine have confirmed and clarified key molecular details of one of these repair systems, known as nucleotide excision repair.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">Using an advanced sequencing technique to map and analyze DNA damage, the scientists demonstrated the functions in bacterial cells of two important excision repair proteins: Mfd and UvrD.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">\u201cThe biochemical mechanisms of these proteins have been known for years from experiments involving purified protein and DNA, and that\u2019s very important, but in this new work we\u2019ve clarified these proteins\u2019 roles in living cells,\u201d said co-senior author Christopher P. Selby, PhD, research assistant professor of biochemistry and biophysics at UNC.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">\u201cUltimately, this better understanding of bacterial DNA repair could be useful toward the development of antibacterial drugs,\u201d said co-senior author Aziz Sancar, MD, PhD, the Sarah Graham Kenan Professor of Biochemistry and Biophysics at UNC.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">The research publishes this week in the<span class=\"Apple-converted-space\"> <\/span><i style=\"margin: 0px; padding: 0px; \">Proceedings of the National Academy of Sciences<\/i>.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">Sancar was awarded the 2015 Nobel Prize for Chemistry for his research in the 1980s and early 1990s on excision repair in bacteria and in human cells. This repair process, which also occurs in animal cells, fixes one of the most common forms of DNA damage: the bulky adduct, an unwanted chemical modification of DNA typically caused by a toxin or ultraviolet (UV) radiation.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">To study excision repair in cells, Sancar, Selby and colleagues recently developed a new technique, XR-seq, which allows investigators to isolate and sequence the small lengths of adduct-damaged DNA that are snipped from the genome during the excision repair process. Knowing the sequences of these DNA snippets allows their locations in the genome to be mapped precisely. They used this method first in 2015 to<span class=\"Apple-converted-space\"> <\/span><a href=\"http:\/\/news.unchealthcare.org\/news\/2015\/may\/unc-researchers-create-dna-repair-map-of-the-entire-human-genome\" style=\"margin: 0px; padding: 0px; color: rgb(153, 65, 0); text-decoration: none; border-bottom: 1px dotted; \">generate a UV repair map of the human genome<\/a>, and in<br style=\"margin: 0px; padding: 0px; \"\/>2016 they used the XR-seq method to generate the damage and repair maps of the anticancer cisplatin drug for the entire human genome. Now they have applied this method to answer some fundamental questions about damage repair in E. coli with the potential of developing novel antibiotic drugs.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \"><b style=\"margin: 0px; padding: 0px; color: rgb(0, 0, 0); \">The un-sticker: Mfd<\/b><\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">In this study, which was also led by postdoctoral research associate Ogun Adebali, PhD, the researchers focused largely on Mfd, a protein known from prior work by Sancar and Selby to have a special \u2013 and mechanistically unusual \u2013 role in excision repair in bacteria.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">\u201cI think Mfd is the most interesting protein in E. coli,\u201d Selby said. Here\u2019s why: When the DNA of a bacterial gene is being transcribed into RNA, and the molecular machinery of transcription gets stuck at a bulky adduct, Mfd appears on the scene, recruits other repair proteins that snip away the damaged section of DNA, and \u201cun-sticks\u201d the transcription machinery so that it can resume its work. This Mfd-guided process is called transcription-coupled repair, and it accounts for a much higher rate of excision repair on strands of DNA that are being actively transcribed.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">Using XR-seq to map UV-induced damage in E. coli bacteria cells, the researchers found clear evidence of transcription-coupled repair in normal cells, but not in cells that lack Mfd, thus confirming the protein\u2019s role in the process.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \"><b style=\"margin: 0px; padding: 0px; color: rgb(0, 0, 0); \">The unwinder: UvrD<\/b><\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">In further experiments, the researchers defined the role of an accessory excision repair protein in E. coli \u2013 UvrD, which helps clear away each excised segment of damaged DNA.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">In the absence of UvrD, the excised piece of DNA remains bound to the chromosomal DNA, making it hard for cellular waste-disposal enzymes to chop it up. At the same time, the repair proteins that excised the strand tend to remain stuck to it, and are thus kept from moving on to excise other bits of damaged DNA. UvrD\u2019s job is to unwind these damaged and discarded strands from chromosomal DNA, so that they can be disposed of quickly and the associated repair proteins can go on to catalyze additional rounds of repair.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">Using XR-seq on UV-damaged E. coli cells, the UNC team confirmed that without UvrD, excised DNA fragments remain stuck to chromosomal DNA, survive much longer in cells, and \u2013 by holding onto excision repair proteins \u2013 slow down the overall rate of excision repair in cells.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">In addition to clarifying the roles of Mfd and UvrD, the research generally heralds the use of the new XR-seq technique in mapping and studying excision repair processes.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">\u201cXR-seq provides a new type of sequence data, and in this work we\u2019ve provided for the first time a genome-wide map of excision repair in a bacterium,\u201d said Adebali. \u201cWe think this map will be broadly useful to the scientific community.\u201d<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">The researchers now plan further studies using XR-seq in bacterial cells, as well as in human and other mammalian cells where the process of excision repair is less understood.<\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \"><i style=\"margin: 0px; padding: 0px; \">Co-authors of the study were postdoctoral researchers Yi-Ying Chiou, PhD, and Jinchuan Hu, PhD, both in the Sancar lab. Aziz Sancar is a member of UNC Lineberger Comprehensive Cancer Center.<\/i><\/p>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \"><i style=\"margin: 0px; padding: 0px; \">The National Institutes of Health funded this research.<\/i><\/p>\n<hr\/>\n<p style=\"margin: 0px 0px 1em; padding: 0px; color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">Story courtesy of <span style=\"color: rgb(50, 50, 50); letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); display: inline !important; float: none; \">Mark Derewicz, 919-923-0959,<span class=\"Apple-converted-space\"> <\/span><\/span><a href=\"mailto:mark.derewicz@unchealth.unc.edu\" style=\"margin: 0px; padding: 0px; color: rgb(153, 65, 0); text-decoration: none; border-bottom: 1px dotted; letter-spacing: normal; text-align: start; text-indent: 0px; text-transform: none; word-spacing: 0px; text-stroke-width: 0px; background-color: rgb(255, 255, 255); \">mark.derewicz@unchealth.unc.edu<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p><!-- description --> <\/p>\n<p class='lead'>Findings come from an advanced DNA sequencing application developed by the lab of University of North Carolina Nobel Laureate Aziz Sancar.<\/p>\n","protected":false},"author":41619,"featured_media":4258,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[34,30,10,28,3,33,4,17],"class_list":["post-4257","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-2017-faculty-year-in-review","tag-2017-year-in-review","tag-news_faculty","tag-news_2017","tag-news_dept","tag-news_faculty_s17","tag-recent-news","tag-sancar_news","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>How Life Survives: UNC researchers confirm basic mechanism of DNA repair | Biochemistry and Biophysics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/biochem\/news\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How Life Survives: UNC researchers confirm basic mechanism of DNA repair | Biochemistry and Biophysics\" \/>\n<meta property=\"og:description\" content=\"Findings come from an advanced DNA sequencing application developed by the lab of University of North Carolina Nobel Laureate Aziz Sancar.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.med.unc.edu\/biochem\/news\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/\" \/>\n<meta property=\"og:site_name\" content=\"Biochemistry and Biophysics\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/uncbiochemistryandbiophysics\/\" \/>\n<meta property=\"article:published_time\" content=\"2017-02-07T10:00:00+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2018-08-01T14:33:16+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2018\/07\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair-image2.jpeg\" \/>\n\t<meta property=\"og:image:width\" content=\"400\" \/>\n\t<meta property=\"og:image:height\" content=\"302\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Carolyn Clabo\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@UNC_BCBP\" \/>\n<meta name=\"twitter:site\" content=\"@UNC_BCBP\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Carolyn Clabo\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/\"},\"author\":{\"name\":\"Carolyn Clabo\",\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/#\/schema\/person\/9693a4e0a76e8208ca2105ae25587332\"},\"headline\":\"How Life Survives: UNC researchers confirm basic mechanism of DNA repair\",\"datePublished\":\"2017-02-07T10:00:00+00:00\",\"dateModified\":\"2018-08-01T14:33:16+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/\"},\"wordCount\":913,\"publisher\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.med.unc.edu\/biochem\/wp-content\/uploads\/sites\/795\/2018\/07\/how-life-survives-unc-researchers-confirm-basic-mechanism-of-dna-repair-image2.jpeg\",\"keywords\":[\"2017-faculty-year-in-review\",\"2017-Year-in-Review\",\"Faculty &amp; 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