{"id":13230,"date":"2020-06-23T09:04:59","date_gmt":"2020-06-23T07:04:59","guid":{"rendered":"https:\/\/idibell.cat\/?p=13230"},"modified":"2020-06-23T09:04:59","modified_gmt":"2020-06-23T07:04:59","slug":"la-biogenesi-dels-ribosomes-pot-detectar-els-nivells-baixos-de-nucleotids-per-preservar-la-integritat-de-ladn","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2020\/06\/la-biogenesi-dels-ribosomes-pot-detectar-els-nivells-baixos-de-nucleotids-per-preservar-la-integritat-de-ladn\/","title":{"rendered":"La biog\u00e8nesi dels ribosomes pot detectar els nivells baixos de nucle\u00f2tids per preservar la integritat de l&#8217;ADN"},"content":{"rendered":"<p>Els tumors creixen molt r\u00e0pidament i, en conseq\u00fc\u00e8ncia, tenen una taxa de replicaci\u00f3 de l&#8217;ADN molt alta per poder dur a terme les divisions cel\u00b7lulars constants. Per aquesta ra\u00f3, molts tractaments antitumorals s&#8217;han centrat a reduir la s\u00edntesi de nucle\u00f2tids, els components b\u00e0sics de l&#8217;ADN, per evitar la replicaci\u00f3 del genoma i, per tant, la divisi\u00f3 cel\u00b7lular. No obstant aix\u00f2, un grup de l&#8217;<a href=\"https:\/\/idibell.cat\/recerca\/area-de-cancer\/programa-de-mecanismes-molleculars-i-terapia-experimental-en-oncologia-oncobell\/metabolisme-i-cancer\/\">IDIBELL<\/a>, acaba de publicar a la revista <a href=\"https:\/\/www.embopress.org\/doi\/full\/10.15252\/embj.2019103838\"><em>EMBO<\/em><\/a> que la manca de nucle\u00f2tids afecta el pas anterior a la replicaci\u00f3 de l&#8217;ADN, quan se sintetitzen les prote\u00efnes necess\u00e0ries per a la replicaci\u00f3 i, en conseq\u00fc\u00e8ncia, aquest proc\u00e9s podria ser objectiu de futurs tractaments.<\/p>\n<p>Aproximadament el 80% dels nucle\u00f2tids s&#8217;incorporen als ribosomes, la maquin\u00e0ria responsable de sintetitzar noves prote\u00efnes, i nom\u00e9s el 15% es convertir\u00e0 en part de l&#8217;ADN. Per replicar l&#8217;ADN d&#8217;una c\u00e8l\u00b7lula tumoral s&#8217;han de sintetitzar totes les prote\u00efnes necess\u00e0ries fer-ho, i aix\u00f2 requerir\u00e0 la s\u00edntesi de nous ribosomes, que al seu torn necessitaran nucle\u00f2tids per formar-se. El grup de Metabolisme i C\u00e0ncer de l&#8217;Institut d&#8217;Investigaci\u00f3 Biom\u00e8dica de Bellvitge (<a href=\"https:\/\/idibell.cat\/recerca\/area-de-cancer\/programa-de-mecanismes-molleculars-i-terapia-experimental-en-oncologia-oncobell\/metabolisme-i-cancer\/\">IDIBELL<\/a>) ha descrit que el proc\u00e9s de biog\u00e8nesi dels ribosomes (s\u00edntesi de nous ribosomes) pot detectar una caiguda en els nivells de nucle\u00f2tids i aturar la divisi\u00f3 cel\u00b7lular abans que comenci la fase de replicaci\u00f3 de l&#8217;ADN. &#8220;Aquest sembla ser un mecanisme important de control&#8221;, diu Joffrey Pelletier, primer autor de l&#8217;article, i afegeix, &#8220;aquest mecanisme evita que la c\u00e8l\u00b7lula repliqui l&#8217;ADN en una situaci\u00f3 transit\u00f2ria de nucle\u00f2tids baixos, el que podria acabar amb dany en l&#8217;ADN &#8220;. Paradoxalment, si persisteix la manca de nucle\u00f2tids, la c\u00e8l\u00b7lula pot perdre aquest mecanisme de control i iniciar la fase de replicaci\u00f3, encara que aquesta ser\u00e0 lenta i imprecisa, causant danys a l&#8217;ADN i inestabilitat gen\u00f2mica.<\/p>\n<p>&nbsp;<\/p>\n<h3>La proposta d&#8217;un nou objectiu antitumoral<\/h3>\n<p>Per reduir les reserves de nucle\u00f2tids, els autors combinen models gen\u00e8tics i farmacol\u00f2gics per inhibir l&#8217;acci\u00f3 de l&#8217;enzim IMPDH, un enzim limitant en la s\u00edntesi de nucle\u00f2tids. Els seus resultats mostren que la inhibici\u00f3 d&#8217;aquest enzim impedeix la replicaci\u00f3 de l&#8217;ADN. L&#8217;estudi tamb\u00e9 mostra que, amb un elevat nivell d&#8217;inhibici\u00f3 del mateix enzim, la c\u00e8l\u00b7lula pot perdre aquest punt de control i permetre la replicaci\u00f3. Per tant, definir la dosi emprada seria important per aplicar el f\u00e0rmac cl\u00ednicament.<\/p>\n<p>&nbsp;<\/p>\n<p>Aquest estudi s&#8217;ha dut a terme gr\u00e0cies a la col\u00b7laboraci\u00f3 del grup de Ram\u00f3n Salazar (OncoBell, <a href=\"http:\/\/ico.gencat.cat\/ca\/inici\/index.html\">ICO<\/a>, Barcelona), \u00d3scar Yanes (IISPV, CIBERDEM, Tarragona) i Neus Agell (IDIBAPS, Barcelona).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Quan els nivells de nucle\u00f2tids cauen, fet molt com\u00fa en l&#8217;inici dels c\u00e0ncers agressius, la biog\u00e8nesi dels ribosomes \u00e9s capa\u00e7 de detectar i prevenir la replicaci\u00f3 de l&#8217;ADN, ja que aix\u00f2 podria causar dany en el genoma.<\/p>\n","protected":false},"author":8,"featured_media":13231,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"default","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[332,408,447],"tags":[],"publishpress_future_action":{"enabled":false,"date":"2024-05-09 20:39:53","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/13230"}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=13230"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/13230\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/13231"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=13230"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=13230"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=13230"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}