HNRNPU facilitates antibody class-switch recombination through C-NHEJ promotion and R-loop suppression.
Cell Rep
; 42(3): 112284, 2023 03 28.
Article
in En
| MEDLINE
| ID: mdl-36943867
ABSTRACT
B cells generate functionally different classes of antibodies through class-switch recombination (CSR), which requires classical non-homologous end joining (C-NHEJ) to join the DNA breaks at the donor and acceptor switch (S) regions. We show that the RNA-binding protein HNRNPU promotes C-NHEJ-mediated S-S joining through the 53BP1-shieldin DNA-repair complex. Notably, HNRNPU binds to the S region RNA/DNA G-quadruplexes, contributing to regulating R-loop and single-stranded DNA (ssDNA) accumulation. HNRNPU is an intrinsically disordered protein that interacts with both C-NHEJ and R-loop complexes in an RNA-dependent manner. Strikingly, recruitment of HNRNPU and the C-NHEJ factors is highly sensitive to liquid-liquid phase separation inhibitors, suggestive of DNA-repair condensate formation. We propose that HNRNPU facilitates CSR by forming and stabilizing the C-NHEJ ribonucleoprotein complex and preventing excessive R-loop accumulation, which otherwise would cause persistent DNA breaks and aberrant DNA repair, leading to genomic instability.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA-Binding Proteins
/
R-Loop Structures
Language:
En
Journal:
Cell Rep
Year:
2023
Document type:
Article
Affiliation country:
Egypt