Electronic Resource
Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids
العنوان: | Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids |
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المؤلفون: | Stoy, Henriette; https://orcid.org/0000-0002-2943-414X, Zwicky, Katharina, Kuster, Danina, Lang, Kevin S, Krietsch, Jana, Crossley, Magdalena P, Schmid, Jonas A; https://orcid.org/0000-0003-1791-1874, Cimprich, Karlene A; https://orcid.org/0000-0002-1937-2969, Merrikh, Houra; https://orcid.org/0000-0001-9956-9640, Lopes, Massimo; https://orcid.org/0000-0003-3847-8133 |
المصدر: | Stoy, Henriette; Zwicky, Katharina; Kuster, Danina; Lang, Kevin S; Krietsch, Jana; Crossley, Magdalena P; Schmid, Jonas A; Cimprich, Karlene A; Merrikh, Houra; Lopes, Massimo (2023). Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids. Nature Structural & Molecular Biology, 30(3):348-359. |
بيانات النشر: | Nature Publishing Group 2023-03-02 |
نوع الوثيقة: | Electronic Resource |
مستخلص: | Transcription-replication collisions (TRCs) are crucial determinants of genome instability. R-loops were linked to head-on TRCs and proposed to obstruct replication fork progression. The underlying mechanisms, however, remained elusive due to the lack of direct visualization and of non-ambiguous research tools. Here, we ascertained the stability of estrogen-induced R-loops on the human genome, visualized them directly by electron microscopy (EM), and measured R-loop frequency and size at the single-molecule level. Combining EM and immuno-labeling on locus-specific head-on TRCs in bacteria, we observed the frequent accumulation of DNA:RNA hybrids behind replication forks. These post-replicative structures are linked to fork slowing and reversal across conflict regions and are distinct from physiological DNA:RNA hybrids at Okazaki fragments. Comet assays on nascent DNA revealed a marked delay in nascent DNA maturation in multiple conditions previously linked to R-loop accumulation. Altogether, our findings suggest that TRC-associated replication interference entails transactions that follow initial R-loop bypass by the replication fork. |
مصطلحات الفهرس: | Institute of Molecular Cancer Research, 570 Life sciences; biology, 610 Medicine & health, Journal Article, PeerReviewed, info:eu-repo/semantics/article, info:eu-repo/semantics/publishedVersion |
URL: | 10.1038/s41594-023-00928-6 |
الاتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess Creative Commons: Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
ملاحظة: | application/pdf info:doi/10.5167/uzh-231952 English English |
Other Numbers: | CHUZH oai:www.zora.uzh.ch:231952 https://www.zora.uzh.ch/id/eprint/231952/1/s41594_023_00928_6.pdf info:doi/10.5167/uzh-231952 info:doi/10.1038/s41594-023-00928-6 info:pmid/36864174 urn:issn:1545-9985 1443051949 |
المصدر المساهم: | HAUPTBIBLIOTHEK UNIV OF ZURICH From OAIster®, provided by the OCLC Cooperative. |
رقم الانضمام: | edsoai.on1443051949 |
قاعدة البيانات: | OAIster |
الوصف غير متاح. |