APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining

Sara De Bragança, Clara Aicart-Ramos, Raquel Arribas-Bosacoma, Angel Rivera-Calzada, Juan Pablo Unfried, Laura Prats-Mari, Mikel Marin-Baquero, Puri Fortes, Oscar Llorca*, Fernando Moreno-Herrero

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The synapsis of DNA ends is a critical step for the repair of double-strand breaks by non-homologous end joining (NHEJ). This is performed by a multicomponent protein complex assembled around Ku70-Ku80 heterodimers and regulated by accessory factors, including long non-coding RNAs, through poorly understood mechanisms. Here, we use magnetic tweezers to investigate the contributions of core NHEJ proteins and APLF and lncRNA NIHCOLE to DNA synapsis. APLF stabilizes DNA end bridging and, together with Ku70-Ku80, establishes a minimal complex that supports DNA synapsis for several minutes under piconewton forces. We find the C-terminal acidic region of APLF to be critical for bridging. NIHCOLE increases the dwell time of the synapses by Ku70-Ku80 and APLF. This effect is further enhanced by a small and structured RNA domain within NIHCOLE. We propose a model where Ku70-Ku80 can simultaneously bind DNA, APLF, and structured RNAs to promote the stable joining of DNA ends.

Original languageEnglish
Article number111917
Number of pages21
JournalCell Reports
Volume42
Issue number1
DOIs
Publication statusPublished - 31 Jan 2023

Keywords / Materials (for Non-textual outputs)

  • APLF
  • CP: Molecular biology
  • DNA ligase IV
  • Ku70-Ku80
  • lncRNA
  • magnetic tweezers
  • NHEJ
  • non-homologous end joining
  • single-molecule
  • XLF
  • Xrcc4

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