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Article: Mechanism of efficient double-strand break repair by a long non-coding RNA

TitleMechanism of efficient double-strand break repair by a long non-coding RNA
Authors
Issue Date2020
Citation
Nucleic Acids Research, 2020, v. 48, n. 19, p. 10953-10972 How to Cite?
AbstractMechanistic studies in DNA repair have focused on roles of multi-protein DNA complexes, so how long non-coding RNAs (lncRNAs) regulate DNA repair is less well understood. Yet, lncRNA LINP1 is over-expressed in multiple cancers and confers resistance to ionizing radiation and chemotherapeutic drugs. Here, we unveil structural and mechanistic insights into LINP1's ability to facilitate non-homologous end joining (NHEJ). We characterized LINP1 structure and flexibility and analyzed interactions with the NHEJ factor Ku70/Ku80 (Ku) and Ku complexes that direct NHEJ. LINP1 self-assembles into phase-separated condensates via RNA-RNA interactions that reorganize to form filamentous Ku-containing aggregates. Structured motifs in LINP1 bind Ku, promoting Ku multimerization and stabilization of the initial synaptic event for NHEJ. Significantly, LINP1 acts as an effective proxy for PAXX. Collective results reveal how lncRNA effectively replaces a DNA repair protein for efficient NHEJ with implications for development of resistance to cancer therapy.
Persistent Identifierhttp://hdl.handle.net/10722/336045
ISSN
2023 Impact Factor: 16.6
2023 SCImago Journal Rankings: 7.048
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorThapar, Roopa-
dc.contributor.authorWang, Jing L.-
dc.contributor.authorHammel, Michal-
dc.contributor.authorYe, Ruiqiong-
dc.contributor.authorLiang, Ke-
dc.contributor.authorSun, Chengcao-
dc.contributor.authorHnizda, Ales-
dc.contributor.authorLiang, Shikang-
dc.contributor.authorMaw, Su S.-
dc.contributor.authorLee, Linda-
dc.contributor.authorVillarreal, Heather-
dc.contributor.authorForrester, Isaac-
dc.contributor.authorFang, Shujuan-
dc.contributor.authorTsai, Miaw Sheue-
dc.contributor.authorBlundell, Tom L.-
dc.contributor.authorDavis, Anthony J.-
dc.contributor.authorLin, Chunru-
dc.contributor.authorLees-Miller, Susan P.-
dc.contributor.authorStrick, Terence R.-
dc.contributor.authorTainer, John A.-
dc.date.accessioned2024-01-15T08:22:18Z-
dc.date.available2024-01-15T08:22:18Z-
dc.date.issued2020-
dc.identifier.citationNucleic Acids Research, 2020, v. 48, n. 19, p. 10953-10972-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/336045-
dc.description.abstractMechanistic studies in DNA repair have focused on roles of multi-protein DNA complexes, so how long non-coding RNAs (lncRNAs) regulate DNA repair is less well understood. Yet, lncRNA LINP1 is over-expressed in multiple cancers and confers resistance to ionizing radiation and chemotherapeutic drugs. Here, we unveil structural and mechanistic insights into LINP1's ability to facilitate non-homologous end joining (NHEJ). We characterized LINP1 structure and flexibility and analyzed interactions with the NHEJ factor Ku70/Ku80 (Ku) and Ku complexes that direct NHEJ. LINP1 self-assembles into phase-separated condensates via RNA-RNA interactions that reorganize to form filamentous Ku-containing aggregates. Structured motifs in LINP1 bind Ku, promoting Ku multimerization and stabilization of the initial synaptic event for NHEJ. Significantly, LINP1 acts as an effective proxy for PAXX. Collective results reveal how lncRNA effectively replaces a DNA repair protein for efficient NHEJ with implications for development of resistance to cancer therapy.-
dc.languageeng-
dc.relation.ispartofNucleic Acids Research-
dc.titleMechanism of efficient double-strand break repair by a long non-coding RNA-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/nar/gkaa784-
dc.identifier.pmid33045735-
dc.identifier.scopuseid_2-s2.0-85095799497-
dc.identifier.volume48-
dc.identifier.issue19-
dc.identifier.spage10953-
dc.identifier.epage10972-
dc.identifier.eissn1362-4962-
dc.identifier.isiWOS:000606018400030-

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