{"id":31614,"date":"2023-02-08T11:40:57","date_gmt":"2023-02-08T09:40:57","guid":{"rendered":"https:\/\/irb.usi.ch\/?p=31614"},"modified":"2023-02-20T17:50:43","modified_gmt":"2023-02-20T15:50:43","slug":"identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination","status":"publish","type":"post","link":"https:\/\/irb.usi.ch\/it\/news\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\/","title":{"rendered":"Identification of a new PLK1-mediated pathway to limit homologous recombination"},"content":{"rendered":"<p><strong>Homologous recombination (HR) could be deleterious when cells are about to undergo division. The Cejka laboratory at the IRB identified a new PLK1-mediated mechanism, which down-regulates DNA end resection late in the cell cycle and hence prevents undesirable HR initiation.<\/strong><\/p>\n<p>Bellinzona, February 8, 2023 &#8211; DNA double-strand break (DSB) repair is initiated by DNA end resection, during which CtIP stimulates the initial processing of the DSB by the MRE11-RAD50-NBS1 (MRN) complex and later the DNA2 helicase-nuclease to extend the resection tracks.<\/p>\n<p>In the current study just published in Genes &amp; Development, Ceppi and colleagues identified a CtIP separation of function mutant, which is still proficient in conjunction with MRN, but is not able to stimulate DNA degradation by DNA2. In cellular experiments, the mutant exhibits lower rates of DNA end resection resulting in increased sensitivity to DSB-inducing drugs. The interplay of CtIP and DNA2 is regulated by phosphorylation. CtIP appears to be targeted by the PLK1 kinase that disrupts DNA2 activation and hence attenuates resection.<\/p>\n<p>The study supports a model where the known CDK kinase-dependent phosphorylation of CtIP activates resection by MRN in S-phase, when sister chromatids are available for the accurate repair of the DSB. Later when cells are about to divide (G2\/M phase), PLK1-mediated phosphorylation of CtIP disrupts resection to allow alternative template-independent repair pathways.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Homologous recombination (HR) could be deleterious when cells are about to undergo division. The Cejka laboratory at the IRB identified a new PLK1-mediated mechanism, which down-regulates DNA end resection late in the cell cycle and hence prevents undesirable HR initiation. Bellinzona, February 8, 2023 &#8211; DNA double-strand break (DSB) repair is initiated by DNA end [&hellip;]<\/p>\n","protected":false},"author":136,"featured_media":31616,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[16,47],"tags":[],"class_list":["post-31614","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","category-press-release"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Identification of a new PLK1-mediated pathway to limit homologous recombination - IRB USI<\/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:\/\/irb.usi.ch\/it\/news\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\/\" \/>\n<meta property=\"og:locale\" content=\"it_IT\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Identification of a new PLK1-mediated pathway to limit homologous recombination - IRB USI\" \/>\n<meta property=\"og:description\" content=\"Homologous recombination (HR) could be deleterious when cells are about to undergo division. The Cejka laboratory at the IRB identified a new PLK1-mediated mechanism, which down-regulates DNA end resection late in the cell cycle and hence prevents undesirable HR initiation. Bellinzona, February 8, 2023 &#8211; DNA double-strand break (DSB) repair is initiated by DNA end [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/irb.usi.ch\/it\/news\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\/\" \/>\n<meta property=\"og:site_name\" content=\"IRB USI\" \/>\n<meta property=\"article:published_time\" content=\"2023-02-08T09:40:57+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2023-02-20T15:50:43+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/irb.usi.ch\/images\/IRB-PCE.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"2358\" \/>\n\t<meta property=\"og:image:height\" content=\"1313\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Andrea Nava\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Scritto da\" \/>\n\t<meta name=\"twitter:data1\" content=\"Andrea Nava\" \/>\n\t<meta name=\"twitter:label2\" content=\"Tempo di lettura stimato\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minuto\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/news\\\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/news\\\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\\\/\"},\"author\":{\"name\":\"Andrea Nava\",\"@id\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/#\\\/schema\\\/person\\\/01bacbaaa75ea23cfc275a8fb0e0ab94\"},\"headline\":\"Identification of a new PLK1-mediated pathway to limit homologous recombination\",\"datePublished\":\"2023-02-08T09:40:57+00:00\",\"dateModified\":\"2023-02-20T15:50:43+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/news\\\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\\\/\"},\"wordCount\":232,\"publisher\":{\"@id\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/news\\\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/irb.usi.ch\\\/images\\\/IRB-PCE.jpg\",\"articleSection\":[\"News\",\"Press release\"],\"inLanguage\":\"it-IT\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/news\\\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\\\/\",\"url\":\"https:\\\/\\\/irb.usi.ch\\\/it\\\/news\\\/identification-of-a-new-plk1-mediated-pathway-to-limit-homologous-recombination\\\/\",\"name\":\"Identification of a new PLK1-mediated pathway to limit homologous recombination - 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The Cejka laboratory at the IRB identified a new PLK1-mediated mechanism, which down-regulates DNA end resection late in the cell cycle and hence prevents undesirable HR initiation. 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