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Nucleostemin promotes RAD51 filament assembly on double-stranded DNA to protect stalled replication forks.

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Τίτλος: Nucleostemin promotes RAD51 filament assembly on double-stranded DNA to protect stalled replication forks.
Συγγραφείς: Chang CC; Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan., Tsai SS; Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan., Chou CL; Department of Chemistry, National Taiwan University, Taipei 106, Taiwan.; Department of Pharmacy, National Taiwan University, Taipei 106, Taiwan., Chang YH; Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan., Hung CT; Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan., Tsai RYL; Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, United States.; Department of Translational Medical Sciences, College of Medicine, Texas A&M University Health Science Center, Houston, TX 77030, United States., Li HW; Department of Chemistry, National Taiwan University, Taipei 106, Taiwan., Liaw H; Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan., Chi P; Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.; Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Πηγή: Nucleic acids research [Nucleic Acids Res] 2026 Aug 10; Vol. 54 (15).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
Imprint Name(s): Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
Ιατρικοί όροι (MeSH): Rad51 Recombinase*/metabolism , Rad51 Recombinase*/genetics , DNA Replication*/genetics , DNA*/metabolism , DNA*/genetics , GTP-Binding Proteins*/metabolism , GTP-Binding Proteins*/genetics , Nuclear Proteins*/metabolism , Nuclear Proteins*/genetics, MRE11 Homologue Protein/metabolism ; MRE11 Homologue Protein/genetics ; DNA-Binding Proteins/metabolism ; Hydroxyurea/pharmacology ; DNA, Single-Stranded/metabolism ; DNA, Single-Stranded/genetics ; Humans
Περίληψη: Replication stress threatens genome integrity by stalling replication forks, which may lead to double-stranded DNA (dsDNA) breaks. Stalled replication forks can be rescued through the fork reversal mechanism, yet they remain vulnerable to nucleolytic attack. Here, we identify nucleostemin (NS/GNL3) as a critical fork-stabilizing factor. We show that NS rapidly accumulates at hydroxyurea-stalled forks and is indispensable for protecting reversed forks, with NS depletion abolishing RAD51 foci formation and unleashing MRE11-mediated degradation. Through biochemical reconstitution and single-molecule fluorescence resonance energy transfer (FRET), we demonstrate that NS binds DNA directly, engages RAD51, and promotes nucleoprotein filament assembly on the dsDNA segment adjacent to the single-stranded DNA/dsDNA junction. This NS-RAD51 complex synergistically shields nascent strands from MRE11-mediated nucleolytic attack. Our work uncovers a new mechanism of fork protection and positions NS as a key guardian of genome integrity under replication stress.
(© The Author(s) 2026. Published by Oxford University Press.)
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Grant Information: Academia Sinica; National Taiwan University; NSTC 114-2326-B-002-006 National Science and Technology Council; NSTC 112-2326-B-002-009 National Science and Technology Council; 114-2123-M-002-008 National Science and Technology Council; NSTC 112-2326-B-006-002 National Science and Technology Council; NSTC 113-2311-B-006-004 National Science and Technology Council; CPRIT RP200081 Cancer Prevention and Research Institute of Texas
Substance Nomenclature: EC 2.7.7.- (Rad51 Recombinase)
9007-49-2 (DNA)
EC 3.6.1.- (GTP-Binding Proteins)
0 (GNL3 protein, human)
0 (Nuclear Proteins)
EC 3.1.- (MRE11 Homologue Protein)
0 (DNA-Binding Proteins)
X6Q56QN5QC (Hydroxyurea)
0 (DNA, Single-Stranded)
0 (MRE11 protein, human)
EC 2.7.7.- (RAD51 protein, human)
Entry Date(s): Date Created: 20260810 Date Completed: 20260810 Latest Revision: 20260813
Update Code: 20260814
PubMed Central ID: PMC13454837
DOI: 10.1093/nar/gkag773
PMID: 42573072
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1362-4962
DOI:10.1093/nar/gkag773