{"id":2091,"date":"2011-04-21T00:00:00","date_gmt":"2011-04-21T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/"},"modified":"2011-04-21T00:00:00","modified_gmt":"2011-04-21T07:00:00","slug":"a-new-ending-to-an-old-tail","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/a-new-ending-to-an-old-tail\/","title":{"rendered":"A new ending to an old &#8220;tail&#8221;"},"content":{"rendered":"<p>LA JOLLA, CA\u2014In stark contrast to normal cells, which only divide a finite number of times before they enter into a permanent state of growth arrest or simply die, cancer cells never cease to proliferate. Now, scientists at the Salk Institute for Biological Studies have uncovered an important clue to one of the mechanisms underlying cancer cell immortality.\n<\/p>\n<p>\nTheir findings, published in the April 22, 2011 issue of <em>Molecular Cell<\/em>, reveal an unanticipated structure at chromosome ends, which could be a key ingredient in the biological &#8220;elixir of life,&#8221; potentially making it an attractive chemotherapeutic target to cut short the life of a cancer cell.\n<\/p>\n<p>\n&#8220;How tumor cells evade cell death is still baffling to us, but we think we may have solved a small piece of this puzzle,&#8221; says <a href=\"\/de\/faculty\/karlseder.html\/\">Jan Karlseder<\/a>, Ph.D., a professor in the Molecular and Cell Biology Laboratory, who led the Salk team.\n<\/p>\n<p>\nA lynchpin to the immortality of malignant cells is the ability to maintain telomeres, the specialized ends of chromosomes. Like slow-burning fuses, telomeres become shorter each time a cell divides, acting as a kind of cellular clock ticking down a cell&#8217;s age. Eventually they are depleted, and the cell enters a permanently arrested state called senescence. To escape this inevitable demise, about 90 percent of human tumors rely on a huge boost in the levels of an enzyme called telomerase, which adds DNA to telomeres, thus turning the clock backwards.\n<\/p>\n<div class=\"imageCaption\"><img decoding=\"async\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2011\/01\/Merge-APBs.jpg\" alt=\"PML bodies that contain telomeric DNA and associated telomere-binding proteins\" width=\"300\"><\/p>\n<p>About 10 percent of tumor cells use a mechanism called ALT, short for alternative lengthening of telomeres, to keep their chromosomes ends intact. PML bodies that contain telomeric DNA and associated telomere-binding proteins (shown in orange) are highly characteristic of ALT tumor cells.\n<\/p>\n<p>\nImage: Courtesy of Dr. Liana Oganesian, Salk Institute for Biological Studies\n<\/p>\n<\/div>\n<p>\nThe remaining 10 percent use a mechanism known as ALT, short for alternative lengthening of telomeres. &#8220;Although it is a rare phenomenon, understanding ALT is essential since tumors can evade anti-cancer therapies aimed at inhibiting the activity of telomerase through the activation of ALT,&#8221; explains postdoctoral researcher and first author Liana Oganesian, Ph.D. &#8220;This is why we clearly need a two-pronged approached to successfully tackle cancer.&#8221;\n<\/p>\n<p>\nUnlike telomerase, which tacks on telomeric DNA, ALT replenishes chromosome ends through a process called homologous recombination. In normal cells homologous recombination is used to mend broken DNA, whereby the intact neighboring DNA of an identical sequence is used as a template to restore the sequence of the broken DNA piece. Uniquely, human ALT tumors make use of the same recombination machinery to illicitly restore lost telomeric DNA, but not much is known about this process.\n<\/p>\n<p>\nTrying to learn more about the biological tools that ALT tumors use to sustain their immortal status, Karlseder and his team uncovered a new structural beacon, called the C-tail-a string of DNA rich in the base cytosine (C) that hangs over the very tip of telomeres. The finding came as a big surprise since conventional wisdom had it that mammalian cells normally terminate both ends of every chromosome with a single-stranded stretch of DNA rich in the base guanine (G).\n<\/p>\n<p>\nWhen Ogenesian carefully looked at chromosome ends, however, she discovered that about half of all telomeres in ALT tumors bore a C-tail, while the presence of such a tail in normal human cells was several hundred fold less prevalent. &#8220;This piece of DNA is conspicuously absent in tumors that use telomerase, suggesting that C-tails are a unique feature of ALT tumors,&#8221; she says.\n<\/p>\n<p>\nCuriously, there is precedent for chromosomal C-tails in an evolutionarily distant relative, the roundworm. In 2008,<br \/>\nthe Karlseder team discovered that G-tails and C-tails happily coexisted in worm cells and went on to show that they team up with two distinct proteins. When the C-tail specific protein was removed from cells, strikingly the worm began to exhibit some of the characteristics normally attributed to human ALT tumors.\n<\/p>\n<p>\n&#8220;It was really exciting to discover that worms can teach us a thing or two about the mechanisms of human cancer,&#8221; says Karlseder and adds that &#8220;the challenge now is to determine the precise role of C-tails in tumor cells and to unveil the mechanisms responsible for creating them.&#8221;\n<\/p>\n<p>\nThe work was funded in part by the National Institutes of Health and a Merieux Research Grant by the Institut Merieux.\n<\/p>\n<p>\n<em>Liana Oganesian<\/em>\n <\/p>\n<p><strong><br \/>\n\u00dcber das Salk Institute for Biological Studies:<\/strong><br \/>\nDas Salk Institute for Biological Studies ist eine der weltweit f\u00fchrenden Institutionen f\u00fcr Grundlagenforschung, an der international renommierte Fakult\u00e4tsmitglieder grundlegende Fragen der Biowissenschaften in einem einzigartigen, kollaborativen und kreativen Umfeld untersuchen. Mit dem Fokus auf Entdeckungen und die Ausbildung zuk\u00fcnftiger Forschergenerationen leisten Salk-Wissenschaftler bahnbrechende Beitr\u00e4ge zu unserem Verst\u00e4ndnis von Krebs, Alterung, Alzheimer, Diabetes und Infektionskrankheiten durch die Untersuchung von Neurowissenschaften, Genetik, Zell- und Pflanzenbiologie sowie verwandten Disziplinen.\n<\/p>\n<p>\nDie Leistungen der Fakult\u00e4t wurden mit zahlreichen Auszeichnungen gew\u00fcrdigt, darunter Nobelpreise und Mitgliedschaften in der National Academy of Sciences. Das 1960 vom Polio-Impfstoff-Pionier Dr. Jonas Salk gegr\u00fcndete Institut ist eine unabh\u00e4ngige gemeinn\u00fctzige Organisation und ein architektonisches Wahrzeichen.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[69],"disease-research":[],"class_list":["post-2091","disclosure","type-disclosure","status-publish","hentry","faculty-jan-karlseder"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>A new ending to an old &quot;tail&quot; - Salk Institute for Biological Studies<\/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.salk.edu\/de\/news-release\/a-new-ending-to-an-old-tail\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A new ending to an old &quot;tail&quot; - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA, CA\u2014In stark contrast to normal cells, which only divide a finite number of times before they enter into a permanent state of growth arrest or simply die, cancer cells never cease to proliferate. Now, scientists at the Salk Institute for Biological Studies have uncovered an important clue to one of the mechanisms underlying cancer cell immortality.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/de\/news-release\/a-new-ending-to-an-old-tail\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"628\" \/>\n\t<meta property=\"og:image:height\" content=\"329\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/\",\"name\":\"A new ending to an old \\\"tail\\\" - Salk Institute for Biological Studies\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2011\\\/01\\\/Merge-APBs.jpg\",\"datePublished\":\"2011-04-21T07:00:00+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/#breadcrumb\"},\"inLanguage\":\"de-DE\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"de-DE\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2011\\\/01\\\/Merge-APBs.jpg\",\"contentUrl\":\"https:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2011\\\/01\\\/Merge-APBs.jpg\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/a-new-ending-to-an-old-tail\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/www.salk.edu\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"A new ending to an old &#8220;tail&#8221;\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#website\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"name\":\"Salk Institute for Biological Studies\",\"description\":\"The Power of Science\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.salk.edu\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"de-DE\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#organization\",\"name\":\"Salk Institute for Biological Studies\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"de-DE\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"contentUrl\":\"http:\\\/\\\/www.salk.edu\\\/wp-content\\\/uploads\\\/2023\\\/03\\\/salk_logo_696.jpg\",\"width\":696,\"height\":696,\"caption\":\"Salk Institute for Biological Studies\"},\"image\":{\"@id\":\"https:\\\/\\\/www.salk.edu\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"A new ending to an old \"tail\" - Salk Institute for Biological Studies","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.salk.edu\/de\/news-release\/a-new-ending-to-an-old-tail\/","og_locale":"de_DE","og_type":"article","og_title":"A new ending to an old \"tail\" - Salk Institute for Biological Studies","og_description":"LA JOLLA, CA\u2014In stark contrast to normal cells, which only divide a finite number of times before they enter into a permanent state of growth arrest or simply die, cancer cells never cease to proliferate. Now, scientists at the Salk Institute for Biological Studies have uncovered an important clue to one of the mechanisms underlying cancer cell immortality.","og_url":"https:\/\/www.salk.edu\/de\/news-release\/a-new-ending-to-an-old-tail\/","og_site_name":"Salk Institute for Biological Studies","og_image":[{"width":628,"height":329,"url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk-institute-preview-image.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"4 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/","url":"https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/","name":"A new ending to an old \"tail\" - Salk Institute for Biological Studies","isPartOf":{"@id":"https:\/\/www.salk.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/#primaryimage"},"image":{"@id":"https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/#primaryimage"},"thumbnailUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2011\/01\/Merge-APBs.jpg","datePublished":"2011-04-21T07:00:00+00:00","breadcrumb":{"@id":"https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/#breadcrumb"},"inLanguage":"de-DE","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/"]}]},{"@type":"ImageObject","inLanguage":"de-DE","@id":"https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/#primaryimage","url":"https:\/\/www.salk.edu\/wp-content\/uploads\/2011\/01\/Merge-APBs.jpg","contentUrl":"https:\/\/www.salk.edu\/wp-content\/uploads\/2011\/01\/Merge-APBs.jpg"},{"@type":"BreadcrumbList","@id":"https:\/\/www.salk.edu\/news-release\/a-new-ending-to-an-old-tail\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.salk.edu\/"},{"@type":"ListItem","position":2,"name":"A new ending to an old &#8220;tail&#8221;"}]},{"@type":"WebSite","@id":"https:\/\/www.salk.edu\/#website","url":"https:\/\/www.salk.edu\/","name":"Salk-Institut f\u00fcr biologische Studien","description":"Die Macht der Wissenschaft","publisher":{"@id":"https:\/\/www.salk.edu\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.salk.edu\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"de-DE"},{"@type":"Organization","@id":"https:\/\/www.salk.edu\/#organization","name":"Salk-Institut f\u00fcr biologische Studien","url":"https:\/\/www.salk.edu\/","logo":{"@type":"ImageObject","inLanguage":"de-DE","@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/","url":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","contentUrl":"http:\/\/www.salk.edu\/wp-content\/uploads\/2023\/03\/salk_logo_696.jpg","width":696,"height":696,"caption":"Salk Institute for Biological Studies"},"image":{"@id":"https:\/\/www.salk.edu\/#\/schema\/logo\/image\/"}}]}},"ACF":{"paper_url":"","journal_title":"","paper_author_list":"","paper_title":"","subhead":"","home_photo":"2011\/KarlsederOganesianHeadshot.jpg","listing_photo":"","line_2":"","line_1":"A new ending to an old &quot;tail&quot;"},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure\/2091","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":0,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure\/2091\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/media?parent=2091"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/faculty?post=2091"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disease-research?post=2091"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}