{"id":24692,"date":"2025-06-05T17:20:59","date_gmt":"2025-06-06T00:20:59","guid":{"rendered":"https:\/\/dornsife.usc.edu\/news\/?p=24692"},"modified":"2026-03-04T17:13:20","modified_gmt":"2026-03-05T01:13:20","slug":"protein-droplets-protect-heterochromatin-from-dna-repair-errors","status":"publish","type":"post","link":"https:\/\/dornsife.usc.edu\/news\/stories\/protein-droplets-protect-heterochromatin-from-dna-repair-errors\/","title":{"rendered":"USC Dornsife study reveals how protein droplets help cells master difficult DNA repair"},"content":{"rendered":"\n\n\n    \n                                \n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--article-hero \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--article-hero\"\n    \n      >\n\n    \n<div class=\"inner-wrapper\">\n          \n<div class=\"f--field f--image\">\n\n    \n    \n    \n    \n    \n    \n              \n      <img\n                            data-src=\"https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/06\/Chiolo_Nup98_Top-768x432.jpg\"\n          data-srcset=\"https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/06\/Chiolo_Nup98_Top-1920x1080.jpg 1920w,https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/06\/Chiolo_Nup98_Top-1280x720.jpg 1280w,https:\/\/dornsife.usc.edu\/news\/wp-content\/uploads\/sites\/7\/2025\/06\/Chiolo_Nup98_Top-768x432.jpg 768w\"          data-sizes=\"(min-width:1200px) 75vw, (min-width:768px) 83vw, 100vw\"          class=\"lazyload\"\n        \n                  alt=\"Broken DNA undergoes repair within protein droplets in a cell nucleus\"\n        \n        \n                                      \/>\n\n    \n    \n  \n  \n\n<\/div>\n  \n      <div class=\"image-caption\">\n          \n<div class=\"f--field f--description\">\n\n    \n  Artist\u2019s depiction of a newly discovered cellular mechanism in which protein droplets safeguard regions of the genome that are notably susceptible to DNA repair mistakes. (Illustration: Yekaterina Kadyshevskaya.)\n\n\n<\/div>\n    <\/div>\n  \n  <div class=\"text-wrapper\">\n          <nav aria-label=\"Breadcrumb\" class=\"breadcrumbs\">\n        <ul>\n                      <li><a href=\"\/news\/stories\/\">News<\/a><\/li>\n                      <li><a href=\"\/news\/stories\/\/?category=science-and-technology\">Science and Technology<\/a><\/li>\n                  <\/ul>\n      <\/nav>\n    \n              \n<div class=\"f--field f--page-title\">\n\n    \n  <h1>USC Dornsife study reveals how protein droplets help cells master difficult DNA repair<\/h1>\n\n\n<\/div>\n    \n          <div class=\"subtitle\">\n            \n<div class=\"f--field f--description\">\n\n    \n  Research uncovers a mechanism that protects the genome by avoiding catastrophic errors when repairing breaks in tightly packed DNA, a finding with implications for cancer and aging.\n\n\n<\/div>\n      <\/div>\n    \n           <strong class=\"author-field\"><span >By<\/span><a href=\"mailto:communication@dornsife.usc.edu\">USC Dornsife News<\/a><\/strong>\n    \n          <span class=\"post-date-field\">June 5, 2025<\/span>\n      <\/div>\n<\/div>\n\n\n  <\/div><\/div>\n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--social-share \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--social-share\"\n    \n      >\n\n    \n  <div class=\"content-wrapper\">\n    <span class=\"a2a_kit a2a_kit_size_32 addtoany_list\" style=\"line-height: 32px;\">\n      <span class=\"title\">\n        Share\n      <\/span>\n                        <a class=\"a2a_button_copy_link\" target=\"_blank\" href=\"\/#copy_link\" rel=\"nofollow noopener\" title=\"Link\">\n            <span class=\"a2a_svg a2a_s__default a2a_s_copy_link\">\n              <svg height=\"19\" viewBox=\"0 0 19 19\" width=\"19\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\"><path d=\"m7.43475275 9.52380952-2.17490843 2.26076008c-1.08745421 1.058837-1.68841575 2.518315-1.68841575 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\n<div class=\"f--field f--section-title\">\n\n    \n  <h2>\n          Key findings:\n      <\/h2>\n\n\n<\/div>\n    \n      <ul>\n              <li><p>New research from USC Dornsife scientists reveals how cells fix dangerous DNA damage in hard-to-repair areas of the genome \u2014 a process that, when it goes wrong, can lead to cancer and other life-threating diseases.<\/p>\n<\/li>\n              <li><p>The researchers discovered that a protein called Nup98 helps coordinate DNA repair by moving broken genetic material out of densely packed regions where fixing it is more prone to errors.<\/p>\n<\/li>\n              <li><p>Nup98 forms liquid droplets around the damaged DNA, creating a protected space that keeps out the wrong repair tools and helps prevent harmful genetic mistakes.<\/p>\n<\/li>\n              <li><p>The findings offer new insight into how cells maintain genome stability and may help explain how certain mutations in Nup98 contribute to diseases like acute myeloid leukemia.<\/p>\n<\/li>\n          <\/ul>\n  <\/div>\n  \n\n  <\/div><\/div>\n\n\n\n\n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--rich-text \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--rich-text\"\n    \n      >\n\n    \n      \n<div class=\"f--field f--wysiwyg\">\n\n    \n  <p>When DNA breaks inside the cell, it can spell disaster, especially if the damage occurs in areas of the genome that are difficult to repair. Now, scientists <a href=\"https:\/\/dornsife.usc.edu\/profile\/irene-chiolo\/\">Irene Chiolo<\/a> and <a href=\"https:\/\/dornsife.usc.edu\/profile\/chiara-merigliano\/\">Chiara Merigliano<\/a> at the USC Dornsife College of Letters, Arts and Sciences have discovered that a protein called Nup98, long known for helping traffic molecules in and out of the cell\u2019s nucleus, plays another surprising role: guiding the cell\u2019s most delicate repairs and reducing the risk of genetic mistakes that can lead to cancer. <a href=\"https:\/\/doi.org\/10.1016\/j.molcel.2025.05.012\" target=\"_blank\" rel=\"noopener\">Their findings<\/a> were published in <em>Molecular Cell<\/em>.<\/p>\n<p>With support from the National Institutes of Health, the National Science Foundation, and the American Cancer Society, the researchers revealed that Nup98 forms droplet-like structures deep inside the nucleus. These \u201ccondensates\u201d act as protective bubbles around broken strands of DNA in areas called heterochromatin \u2014 zones where the genetic material is so tightly packed that making accurate repairs is especially challenging.<\/p>\n<p>Heterochromatin \u2014 a major <a href=\"https:\/\/dornsife.usc.edu\/news\/stories\/molecular-biologist-earns-nsf-career-grant-to-study-dna-repair\/\">focus of Chiolo\u2019s research<\/a> \u2014 is filled with repeated DNA sequences, making it easy for the cell to confuse one stretch for another. Nup98\u2019s droplets help lift the damaged section out of that dense zone and create a safer space where it can be repaired accurately, reducing the chance of genetic mix-ups that could lead to cancer.<\/p>\n<p>The researchers also found that Nup98 helps mobilize the damaged site in tightly packed heterochromatin, so it can reach a different part of the nucleus where repair is safer.<\/p>\n<p><strong>Coordinating the repair crew<\/strong><\/p>\n<p>Timing is everything when it comes to DNA repair, and one of Nup98\u2019s most important roles is knowing when to say, \u201cNot yet.\u201d<\/p>\n<p>The protein\u2019s droplet-like condensates act as a temporary shield around damaged DNA, keeping out certain repair proteins that can cause trouble if they arrive too soon. One of those proteins, called Rad51, can accidentally stitch together the wrong pieces of DNA if it gets involved too early in the process.<\/p>\n<p>\u201cThe Nup98 droplets keep Rad51 away until other mechanisms have done their work to line up the correct pieces,\u201d Chiolo said. \u201cOnly once the damaged heterochromatin moves into a different nuclear space, Rad51 can safely finish the repair.\u201d<\/p>\n<p>By coordinating this carefully staged process, Nup98 helps cells avoid dangerous genetic rearrangements \u2014 a key part of maintaining genome stability and slowing processes responsible for cancer and aging.<\/p>\n<p><strong>Implications for cancer and therapy<\/strong><\/p>\n<p>Although the researchers studied cells of fruit flies, the insights gained can help explain how similar DNA repair mechanisms work in humans. Many DNA repair mechanisms in fruit flies are shared across species, making them a powerful model for understanding genome stability.<\/p>\n<p>The Nup98 discovery could have real-world impact, especially for diseases like acute myeloid leukemia, where mutations in Nup98 are known to play a role. By elucidating how Nup98 guides DNA repair, scientists hope to uncover why its mutations are so dangerous \u2014 and how to harness the mutations to disrupt cancer cells in targeted treatments.<\/p>\n<p>\u201cEventually, we may also be able to turn Nup98 mutations that lead to cancer, especially acute myeloid leukemia, into treatment targets \u2014 either by specifically disrupting the cells carrying the mutation or by inactivating the harmful functions of the mutated proteins,\u201d Merigliano said.<\/p>\n<p>The team also sees long-term potential for therapies that could enhance or mimic Nup98\u2019s protective functions, reducing the risk of genome instability, which is a major factor not only in cancer, but also in aging and other genome instability disorders.<\/p>\n<p><strong>About the study<\/strong><\/p>\n<p>The study, which is available for <a href=\"https:\/\/authors.elsevier.com\/a\/1lDFn3vVUPVaQi\" target=\"_blank\" rel=\"noopener\">free download<\/a> through July 9, was an international effort with 17 scientists from seven institutions collaborating.<\/p>\n<p>In addition to Chiolo and Merigliano, study authors include Chetan Rawal, Colby See, Anik Mitra, Trevor Reynolds, Nadejda Butova and Christopher Caridi of USC Dornsife; Taehyun Ryu of USC Dornsife and Harvard University; Xiao Li of USC Dornsife and the University of Calgary, Alberta;\u00a0 Jeff Wang and Patrick Sung of the University of Texas Health Science Center; Changfeng Deng and David Chenoweth of the University of Pennsylvania; Maya Capelson of San Diego State University; and Lum\u00edr Krej\u010d\u00ed and Jakub Cibulka of Masaryk University in the Czech Republic.<\/p>\n<p>The research was supported by the following National Institutes of Health grants: F31ES036878; T32GM118289; P01CA265794; R01AR077094; R01GM124143; T32GM145432; CA148724; R35CA241801; and R01GM117376.<\/p>\n<p>National Science Foundation grants DMR-2309043 and 1751197, American Cancer Society grant ACS RSG-24-1325787-01-DMC, an AAUW International Fellowship, USC Research Enhancement Fellowships, a Rose Hills Foundation Fellowship, and grants from the Czech Science Foundation also supported the research.<\/p>\n<p><em>Editor\u2019s Note: Darrin S. Joy and Jim Key contributed to this article.<\/em><\/p>\n\n\n\n<\/div>\n\n\n  <\/div><\/div>\n\n\n\n  \n        \n  \n    \n\n\n\n\n\n\n<div\n  class=\"cc--component-container cc--article-related-stories \"\n\n  \n  \n  \n  \n  \n  \n  >\n  <div class=\"c--component c--article-related-stories\"\n    \n      >\n\n    \n  <div class=\"inner-wrapper\">\n              \n<div class=\"f--field f--section-title\">\n\n    \n  <h2>\n          Related Articles\n      <\/h2>\n\n\n<\/div>\n    \n                  <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a href=\"https:\/\/youtu.be\/giqbYRVn5v4\" \n         target=\"_blank\"                 class=\"\" \n      >\u2018Trojan Talks\u2019: USC President Beong-Soo Kim talks with Assal Habibi<\/a>\n      <\/h3>\n\n\n<\/div>\n        <\/article>\n              <article>\n              \n<div class=\"f--field f--cta-title\">\n\n    \n  <h3>\n          <a 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aging.<\/p>\n","protected":false},"author":14,"featured_media":24698,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[16],"tags":[81,116,616,60],"class_list":["post-24692","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-and-technology","tag-cancer","tag-genetics-and-genomics","tag-molecular-biology","tag-research"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.1.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>USC Dornsife study reveals how protein droplets help cells master difficult DNA repair<\/title>\n<meta name=\"description\" content=\"USC Dornsife scientist find a hidden method cells use to avoid catastrophic errors when repairing tightly packed DNA\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" 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