Electronic Resource

Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids

التفاصيل البيبلوغرافية
العنوان: Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids
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: https://www.zora.uzh.ch/id/eprint/231952/
https://www.zora.uzh.ch/id/eprint/231952
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
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رقم الانضمام: edsoai.on1443051949
قاعدة البيانات: OAIster