Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 19, Pages 10953-10972Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa784
Keywords
-
Categories
Funding
- National Institutes of Health (NIH) [P01 CA092584, R35 CA220430]
- M.D. Anderson Cancer Center Knowledge GAP Award
- Cancer Prevention Research Institute of Texas (CPRIT) [RP180813, RP130397]
- NIH [1R01 CA218025-01, 1R01CA231011-01, R01 CA162804]
- CPRIT Individual Investigator Research Award [180259]
- Program 'Equipe Labellisee' of the French National League Against Cancer
- PSL University 'NanoRep' grant
- CNRS
- Ecole normale superieure
- China Scholarship Council
- Wellcome Trust [200814/Z/16/Z]
- Robert A. Welch Chemistry Chair
- INSERM
- Cancer Prevention andResearch Institute of Texas
Ask authors/readers for more resources
Mechanistic 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available