Tony Hunter<\/a>, Ph.D., American Cancer Society Professor in the Molecular and Cell Biology Laboratory and director of the Salk Institute Cancer Center, who led the study. “Failure to do so can have disastrous consequences.”\n<\/p>\n\nThe DNA in our cells is under constant attack from reactive chemicals generated as byproducts of cellular metabolism. In addition, it is assaulted by x-rays, ultraviolet radiation from the sun, and environmental carcinogens such as tobacco smoke. As a result of this continuous bombardment, some studies have estimated that the DNA in a single human cell gets damaged over 10,000 times every day.\n<\/p>\n
\nIf not repaired properly, the damage leads to mutations, which over time can cause cancer. “As a result, individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer,” notes first author Zhongsheng You, Ph.D., a former postdoctoral researcher at the Salk Institute and now an assistant professor at Washington University School of Medicine in St. Louis.\n<\/p>\n
\nDNA consists of two intertwined strands so that when the DNA is broken, two ends are revealed, one from each strand. In order to repair the DNA break, one strand is trimmed away\u2014or resected\u2014like a loose thread, leaving only the second strand. This exposed strand then searches for a copy of itself (located on its sister chromosome), and “photocopies” past the broken region, repairing the DNA and zipping itself back up.\n<\/p>\n
\nIn yeast, CtIP is required for resection of the broken end, and since it is also recruited to sites of DNA damage in human cells, Hunter’s team wanted to know whether CtIP plays a similar role there. To find out, they depleted CtIP from human cells and caused DNA damage. Without the CtIP, they discovered, the cells could no longer trim back the damaged DNA strands, which brought the whole repair process to an abrupt halt.\n<\/p>\n
\n“It looks like CtIP recruitment is a very important control point in the DNA repair process,” You observes. “Once CtIP is recruited, resection and repair begin, so regulating CtIP recruitment is one way to regulate DNA repair itself.”\n<\/p>\n
\nIn order to understand the process better, the researchers then asked which regions of the CtIP protein are involved in binding it to the broken DNA ends. By testing small portions of the protein, they found that a region in the central part of CtIP helps recruit the protein. They named this region the “damage recruitment” (DR) domain.\n<\/p>\n
\nFurther studies suggested that the DR domain within CtIP is normally hidden inside the folded protein. Only when the cell sends a DNA damage signal is CtIP’s DR domain exposed, and only then can CtIP bind to the broken DNA. In this way, CtIP is like a switchblade that cells open only in the presence of DNA damage.\n<\/p>\n
\nThe authors believe that exposure of CtIP’s DR domain and its recruitment to the site of DNA damage triggers a chain reaction that results in DNA repair, and they now want to understand exactly what CtIP does to start the DNA repair process.\n<\/p>\n
\nYou is also trying to understand the modifications in CtIP that cause the DR domain to be exposed, and is looking into the role of CtIP in cancer. “Mutations in CtIP have not been mapped extensively in human tumors, but from this data, we predict that mutations to the DR domain would lead to cancer,” he says.\n<\/p>\n
\nIn the long term, the team hopes that a better understanding of the DNA damage pathway may provide clues for cancer treatment in the future. “CtIP is another important player in the double-strand break response,” says Hunter. “We have added another piece to the complex puzzle of DNA repair.”\n<\/p>\n
\nAlong with Drs. Hunter and You, researchers who contributed to the work include Linda Shi, Ph.D. , and Andrew Basilio at the University of California, San Diego; Quan Zhu, Ph.D., Nina Tonnu, and Inder Verma, Ph.D. in the Salk Institute’s Laboratory of Genetics; Peng Wu, Ph.D., in You’s lab at Washington University School of Medicine; You-Wei Zhang, Ph.D. , now at Case Western Reserve University; and Michael W. Berns, Ph.D., at UCSD and University of California, Irvine.\n<\/p>\n
\nClaire Attwooll<\/em>\n<\/p>\nAcerca del Instituto Salk de Estudios Biol\u00f3gicos:<\/strong>
\nEl Instituto Salk de Estudios Biol\u00f3gicos es una de las instituciones de investigaci\u00f3n b\u00e1sica m\u00e1s destacadas del mundo, donde un cuerpo docente de prestigio internacional investiga cuestiones fundamentales de las ciencias de la vida en un entorno \u00fanico, colaborativo y creativo. Centrados tanto en el descubrimiento como en la formaci\u00f3n de las futuras generaciones de investigadores, los cient\u00edficos del Salk realizan contribuciones revolucionarias a nuestra comprensi\u00f3n del c\u00e1ncer, el envejecimiento, el Alzheimer, la diabetes y las enfermedades infecciosas mediante el estudio de la neurociencia, la gen\u00e9tica, la biolog\u00eda celular y vegetal, y otras disciplinas relacionadas.\n<\/p>\n\nLos logros del cuerpo docente han sido reconocidos con numerosos galardones, entre los que se incluyen premios Nobel y la pertenencia a la Academia Nacional de Ciencias. Fundado en 1960 por el Dr. Jonas Salk, pionero en la vacuna contra la poliomielitis, el Instituto es una organizaci\u00f3n independiente sin fines de lucro y un hito arquitect\u00f3nico.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[72],"disease-research":[],"class_list":["post-2014","disclosure","type-disclosure","status-publish","hentry","faculty-tony-hunter"],"acf":[],"yoast_head":"\n
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