{"690506":{"#nid":"690506","#data":{"type":"news","title":"Breakthrough Study Sheds Light on How BRCA\u2011Related Cancers Repair Broken DNA","body":[{"value":"\u003Cp dir=\u0022ltr\u0022\u003E\u003Cem\u003EThis research is shared jointly with the\u0026nbsp;\u003C\/em\u003E\u003Ca href=\u0022https:\/\/news.osu.edu\/best-snapshots-yet-of-dna-repair-protein-relevant-to-brca-mutations\/\u0022\u003E\u003Cem\u003E\u003Cstrong\u003EOhio State University\u003C\/strong\u003E\u003C\/em\u003E\u003C\/a\u003E\u003Cem\u003E newsroom.\u003C\/em\u003E\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EScientists have captured the most detailed structural images to date of a specific type of protein\u2019s DNA repair process. The research could reveal ways to inhibit the effects of the BRCA1 and BRCA2 gene mutations that heighten the risk for breast, ovarian, and other cancers.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003E\u201cThis work lets us see, step by step, one mechanism by which cancer cells could manage to repair their DNA when BRCA genes mutate and fail,\u201d says study co-author\u0026nbsp;\u003Ca href=\u0022https:\/\/chemistry.gatech.edu\/people\/vicki-wysocki\u0022\u003E\u003Cstrong\u003EVicki Wysocki\u003C\/strong\u003E\u003C\/a\u003E,\u003Cstrong\u003E\u0026nbsp;\u003C\/strong\u003Ewho is chair of the Georgia Tech\u0026nbsp;\u003Ca href=\u0022https:\/\/chemistry.gatech.edu\/\u0022\u003ESchool of Chemistry and Biochemistry\u003C\/a\u003E. \u201cBy capturing this process in detail, this study opens the door to understanding how those cancerous cells survive and how treatments might disrupt that mechanism.\u201d\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EDesignated as a Breakthrough Article, the study\u0026nbsp;\u003Ca href=\u0022https:\/\/academic.oup.com\/nar\/article\/54\/8\/gkag320\/8661651?login=false\u0022\u003E\u003Cem\u003EMechanism of single-strand annealing from native mass spectrometry and cryo-EM structures of RAD52 homolog Mgm101\u003C\/em\u003E\u003C\/a\u003E was recently published in \u003Cem\u003ENucleic Acids Research.\u003C\/em\u003E\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EIn addition to Wysocki, who is a professor in the\u0026nbsp;\u003Ca href=\u0022https:\/\/chemistry.gatech.edu\/\u0022\u003ESchool of Chemistry and Biochemistry\u003C\/a\u003E and a professor emerita at Ohio State University, the Georgia Tech research team included co-first author\u0026nbsp;\u003Cstrong\u003EZihao Qi,\u003C\/strong\u003E a Ph.D. candidate in the\u0026nbsp;\u003Ca href=\u0022https:\/\/sites.gatech.edu\/wysocki-group\/\u0022\u003EWysocki Lab\u003C\/a\u003E.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EThey were joined by Ohio State researchers co-first author\u0026nbsp;\u003Ca href=\u0022https:\/\/osbp.osu.edu\/people\/wheat.35\u0022\u003E\u003Cstrong\u003ECarter Wheat\u003C\/strong\u003E\u003C\/a\u003E and senior author\u0026nbsp;\u003Ca href=\u0022https:\/\/medicine.osu.edu\/find-a-researcher\/charles-bell-100003449\u0022\u003E\u003Cstrong\u003ECharles Bell\u003C\/strong\u003E\u003C\/a\u003E, who is a professor of biological chemistry and pharmacology in the \u003Ca href=\u0022https:\/\/medicine.osu.edu\/news#\/search\/brac\u0022\u003ECollege of Medicine\u003C\/a\u003E. Additional authors include Metro High School student\u0026nbsp;\u003Cstrong\u003EMiqdad Hussain\u003C\/strong\u003E and\u0026nbsp;\u003Ca href=\u0022http:\/\/www.cas.org\/\u0022\u003ECAS\u003C\/a\u003E researcher \u003Cstrong\u003EKaterina Zakharova\u003C\/strong\u003E.\u003C\/p\u003E\u003Ch2 dir=\u0022ltr\u0022\u003E\u003Cstrong\u003EWhen BRCA Fails\u003C\/strong\u003E\u003C\/h2\u003E\u003Cp dir=\u0022ltr\u0022\u003ENormally, BRCA genes help prevent cancer by acting as tumor suppressors \u2014 producing proteins that help repair broken DNA. When cancer cells lack the tumor-suppression function of normal BRCA genes, research has shown that a protein called RAD52 performs DNA repair.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003ESince RAD52 allows cancer cells to survive and replicate without tumor suppression, researchers have wondered if blocking it would kill the cancerous cells. Blocking RAD52, however, requires fully understanding its repair activities, which have been difficult to capture with even the most sophisticated techniques.\u0026nbsp;\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EDNA strands break every day in cells, which is why proteins exist to fix the breaks and keep cellular processes running smoothly, the team says. But because repairs must happen quickly and human proteins are often more complex than their ancestral counterparts, even the most advanced imaging equipment can\u2019t capture every step in the process.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EIn order to understand RAD52 better, the research team turned to its ancestral protein, Mgm101, to observe several key steps in its DNA repair process.\u003C\/p\u003E\u003Ch2 dir=\u0022ltr\u0022\u003E\u003Cstrong\u003EA Clearer Image\u003C\/strong\u003E\u003C\/h2\u003E\u003Cp dir=\u0022ltr\u0022\u003EThe team decided to leverage multiple types of imaging. Wysocki\u2019s lab at Georgia Tech conducted native mass spectrometry and mass photometry, using light to measure masses of protein-DNA complexes. The results showed that the ancestral protein Mgm101 assembled from a single copy of itself into a large multi-unit ring composed of 19 copies of the protein.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003E\u201cThis ring is essentially a template,\u201d Wysocki explains. \u201cThe first strand of DNA can come down, and then the second strand comes on and starts being annealed to the first strand.\u201d Annealing occurs when two single strands of DNA come together to form the characteristic double helix structure.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EThe findings were supported by what Bell\u2019s lab determined using cryogenic electron microscopy, observing structures floating in solution and frozen in a thin layer of ice.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003E\u201cRAD52 high-resolution structures have been determined with single-stranded DNA, but not with the two DNAs that it\u2019s trying to anneal,\u201d Bell says. \u201cIts job is to bind single-stranded DNA and anneal it to its complement sequence. It\u2019s been captured structurally, but only in a few states relevant to the reaction.\u201d\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003E\u201cHere, we have more of the states along the full pathway from substrate, to intermediate and product. And the duplex intermediate is a conformation that\u2019s never been seen before.\u201d\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003EPreviously, researchers were unsure if this DNA repair process used one protein ring or two rings working together, the team says. Their findings show that just one ring is used\u0026nbsp;\u2014 and that\u0026nbsp;this is likely consistent across different species.\u003C\/p\u003E\u003Ch2 dir=\u0022ltr\u0022\u003E\u003Cstrong\u003EPaths to Treatment\u003C\/strong\u003E\u003C\/h2\u003E\u003Cp dir=\u0022ltr\u0022\u003ENext, the team plans to try capturing the same phases of the DNA repair process with RAD52 from humans. A clearer understanding of how this family of proteins binds to DNA strands and coaxes them back together after a break provides insights for drug targets that could halt the process in cancer cells empowered by mutated BRCA genes, they say.\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003E\u201cIt\u2019s still a proposed mechanism: Just because we see these snapshots of the process doesn\u2019t mean we know all the details, but we do have the best snapshots for any protein that does this single-strand annealing,\u201d says Bell. \u201cThis focuses our strategies for drug development.\u201d\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003E\u003Cem\u003EDOI:\u0026nbsp;\u003C\/em\u003E\u003Ca href=\u0022https:\/\/doi.org\/10.1093\/nar\/gkag320\u0022\u003E\u003Cem\u003Ehttps:\/\/doi.org\/10.1093\/nar\/gkag320\u003C\/em\u003E\u003C\/a\u003E\u003C\/p\u003E\u003Cp dir=\u0022ltr\u0022\u003E\u003Cem\u003EFunding: This work was supported by the U.S. National Science Foundation and the National Institutes of Health. The cryo-EM data were collected at Ohio State\u2019s Center for Electron Microscopy and Analysis and processed using the Ohio Supercomputer Center.\u003C\/em\u003E\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003E\u003Cem\u003EThe research captures detailed snapshots of a process that helps cancer cells survive \u2014 and may point to new treatments.\u003C\/em\u003E\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"The research captures detailed snapshots of a process that helps cancer cells survive \u2014 and may point to new treatments."}],"uid":"35599","created_gmt":"2026-05-27 13:56:51","changed_gmt":"2026-06-05 16:50:08","author":"sperrin6","boilerplate_text":"","field_publication":"","field_article_url":"","location":"Atlanta, GA","dateline":{"date":"2026-05-27T00:00:00-04:00","iso_date":"2026-05-27T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"680421":{"id":"680421","type":"image","title":"Vicki Wysocki","body":"\u003Cp\u003E\u003Cstrong\u003EVicki Wysocki\u003C\/strong\u003E\u003C\/p\u003E","created":"1780677825","gmt_created":"2026-06-05 16:43:45","changed":"1780677825","gmt_changed":"2026-06-05 16:43:45","alt":"Vicki Wysocki","file":{"fid":"264678","name":"Vicki-Wysocki.jpg","image_path":"\/sites\/default\/files\/2026\/06\/05\/Vicki-Wysocki.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2026\/06\/05\/Vicki-Wysocki.jpg","mime":"image\/jpeg","size":299719,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2026\/06\/05\/Vicki-Wysocki.jpg?itok=coGCKGlG"}}},"media_ids":["680421"],"related_links":[{"url":"https:\/\/news.osu.edu\/best-snapshots-yet-of-dna-repair-protein-relevant-to-brca-mutations\/","title":"Best snapshots yet of DNA repair protein relevant to BRCA mutations"}],"groups":[{"id":"1278","name":"College of Sciences"},{"id":"1188","name":"Research Horizons"},{"id":"85951","name":"School of Chemistry and Biochemistry"}],"categories":[{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"},{"id":"140","name":"Cancer Research"},{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"},{"id":"134","name":"Student and Faculty"}],"keywords":[{"id":"187915","name":"go-researchnews"},{"id":"192250","name":"cos-microbial"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"},{"id":"193653","name":"Georgia Tech Research Institute"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:sperrin6@gatech.edu\u0022\u003ESelena Langner\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003EResearch Writer \/ Editor\u003C\/p\u003E\u003Cp\u003EGeorgia Tech College of Sciences\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}