{"id":1908,"date":"2007-02-14T00:00:00","date_gmt":"2007-02-14T08:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/dna-ends-common-tool-different-job\/"},"modified":"2007-02-14T00:00:00","modified_gmt":"2007-02-14T08:00:00","slug":"dna-ends-common-tool-different-job","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/dna-ends-common-tool-different-job\/","title":{"rendered":"Extremos del ADN: herramienta com\u00fan, trabajo diferente"},"content":{"rendered":"<p>La Jolla, CA \u2013 Cada vez que una c\u00e9lula repara o replica su ADN, la hebra sencilla resultante es envuelta por un complejo proteico dedicado. En eucariotas u organismos cuyas c\u00e9lulas tienen un n\u00facleo, esta tarea es manejada por un complejo tripartito llamado prote\u00edna de replicaci\u00f3n A (RPA, por sus siglas en ingl\u00e9s). Investigadores del Instituto Salk de Estudios Biol\u00f3gicos han descubierto ahora un complejo similar a RPA que se enfoca espec\u00edficamente en el extremo corto de \u201ccola\u201d de ADN de hebra sencilla de los cromosomas de levadura.<\/p>\n<p>Sus hallazgos, reportados en la edici\u00f3n en l\u00ednea de <em>Nature Structural &amp; Molecular Biology<\/em>, ayudar\u00e1 a los cient\u00edficos a comprender mejor la din\u00e1mica que mantiene intactos los extremos de los cromosomas, llamados tel\u00f3meros. <\/p>\n<p>\u201cLa identificaci\u00f3n de este nuevo complejo similar a RPA, que se dirige a una regi\u00f3n espec\u00edfica del genoma, sugiere que han evolucionado m\u00faltiples complejos similares a RPA, cada uno haciendo contribuciones individuales a la estabilidad gen\u00f3mica\u201d, dice el autor principal del estudio. <a href=\"\/es\/faculty\/lundblad.html\/\">Vicki Lundblad<\/a>, Ph.D., profesor del Laboratorio de Biolog\u00eda Celular Molecular del Instituto Salk.<\/p>\n<p>Con cada ronda de divisi\u00f3n celular, los tel\u00f3meros \u2013 largas extensiones de ADN repetitivo \u2013 se erosionan un poco m\u00e1s. Algunos han comparado este acortamiento progresivo con un reloj biol\u00f3gico gen\u00e9tico que se agota con el tiempo. De hecho, cuando los tel\u00f3meros alcanzan una \u201clongitud cr\u00edtica\u201d, la c\u00e9lula ya no puede multiplicarse, un signo caracter\u00edstico de la senescencia celular. <\/p>\n<p>En ciertas c\u00e9lulas, como nuestras c\u00e9lulas germinales o las c\u00e9lulas de levadura de panader\u00eda, que necesitan dividirse indefinidamente, una enzima llamada telomerasa alarga los tel\u00f3meros para compensar el continuo acortamiento en los extremos de los cromosomas. Al mismo tiempo, la actividad de la telomerasa es el principal mecanismo por el cual las c\u00e9lulas tumorales humanas logran un crecimiento inmortal.<\/p>\n<p>Adem\u00e1s, los extremos naturales de los cromosomas podr\u00edan parecer hebras de ADN rotas que la maquinaria de reparaci\u00f3n de una c\u00e9lula est\u00e1 dise\u00f1ada para arreglar. Este ha sido un enigma de larga data, porque reparar los extremos de los cromosomas como si fueran roturas de doble cadena resultar\u00eda en una degradaci\u00f3n no regulada o en fusiones de extremo a extremo. Tales eventos de reparaci\u00f3n son letales para el genoma y, en ciertos entornos, pueden promover el desarrollo del c\u00e1ncer.<\/p>\n<p>Hace aproximadamente 10 a\u00f1os, Lundblad descubri\u00f3 que la Cdc13, una prote\u00edna que se une al ADN telom\u00e9rico de cadena sencilla, desempe\u00f1a un papel central en los tel\u00f3meros de la levadura de panader\u00eda. Pero la funci\u00f3n de dos prote\u00ednas asociadas a Cdc13, Stn1 y Ten1, segu\u00eda sin estar clara.<\/p>\n<p>Cuando los miembros del laboratorio Lundblad buscaron parientes de Stn1 en el Protein Data Bank, desenterraron Rpa2, la subunidad intermedia del complejo RPA. En particular, Stn1 y Rpa2 comparten similitudes en una regi\u00f3n conocida como pliegue de uni\u00f3n a oligonucle\u00f3tidos\/oligosac\u00e1ridos u OB-fold, un pliegue proteico que se utiliza com\u00fanmente para reconocer y unirse a ADN o ARN. <\/p>\n<p>Bas\u00e1ndose en estos hallazgos, Lundblad y sus colegas desarrollaron un modelo, el cual predice que Cdc13, Stn1 y Ten1 se unen en el extremo de los cromosomas para formar un complejo dedicado a los tel\u00f3meros similar al RPA, al que llamaron complejo t-RPA.<\/p>\n<p>La estudiante de posgrado y autora principal Hua Gao puso a prueba este modelo, utilizando detallados experimentos bioqu\u00edmicos que revelaron que Stn1 y Ten1 se comportan de manera similar a sus contrapartes en el complejo RPA convencional. Sin embargo, Stn1 y Ten1 tienen la misma predilecci\u00f3n por el ADN telom\u00e9rico de cadena simple que Cdc13, lo que ayuda a garantizar que este complejo solo se dirija a las puntas de los cromosomas. <\/p>\n<p>Seg\u00fan Lundblad, este hallazgo plantea preguntas importantes sobre los posibles paralelismos biol\u00f3gicos entre el complejo RPA convencional y el complejo t-RPA reci\u00e9n descubierto. <\/p>\n<p>\u201cMientras que el complejo RPA convencional act\u00faa en otra parte del genoma para hacer sonar la alarma y atraer la atenci\u00f3n de la maquinaria de reparaci\u00f3n\u201d, dice Lundblad<em>, <\/em>\u201ccuriosamente, el complejo t-RPA realiza la funci\u00f3n opuesta exacta en los extremos de los cromosomas, asegurando que estas puntas no se conviertan en objetivos para la reparaci\u00f3n del ADN.\u201d<\/p>\n<p>El grupo de Lundblad est\u00e1 trabajando actualmente en la elucidaci\u00f3n de lo que distingue las actividades de estos dos complejos de RPA entre s\u00ed. Entre los investigadores que tambi\u00e9n contribuyeron a este trabajo se encuentran la investigadora postdoctoral Rachel B. Cervantes, Ph.D., y los estudiantes graduados Edward K. Mandell y Joel. H. Otero. <\/p>\n<p>El Instituto Salk de Estudios Biol\u00f3gicos en La Jolla, California, es una organizaci\u00f3n independiente sin fines de lucro dedicada a descubrimientos fundamentales en las ciencias de la vida, la mejora de la salud humana y la formaci\u00f3n de futuras generaciones de investigadores. Jonas Salk, M.D., cuya vacuna contra la polio pr\u00e1cticamente erradic\u00f3 la paralizante enfermedad poliomielitis en 1955, inaugur\u00f3 el Instituto en 1965 con una donaci\u00f3n de terrenos de la ciudad de San Diego y el apoyo financiero de la March of Dimes.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[98],"disease-research":[],"class_list":["post-1908","disclosure","type-disclosure","status-publish","hentry","faculty-vicki-lundblad"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>DNA ends: common tool, different job - 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\/es\/news-release\/dna-ends-common-tool-different-job\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"DNA ends: common tool, different job - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"La Jolla, CA \u2013 Every time a cell repairs or replicates its DNA, the resulting single strand is wrapped up by a dedicated protein complex. 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