APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining
De Bragança S, Aicart-Ramos C, Arribas-Bosacoma R, Rivera-Calzada A, Unfried J P, Prats-Mari L, Marin-Baquero M, Fortes P, Llorca* O and Moreno-Herrero* F.
- In NHEJ, APLF promotes synapsis of DNA ends for several minutes under piconewton forces
- Ku70-Ku80 and APLF establish a minimal complex sufficient to support DNA synapsis
- Long non-coding RNA NIHCOLE stabilizes a DNA synapsis mediated by Ku70-Ku80 and APLF
- A small and structured RNA domain of NIHCOLE promotes stable joining of DNA ends
Abstract: 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.
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