Scientific publications
- [GENE THERAPY AND REGULATION OF GENE EXPRESSION]
- [THERAPEUTIC LONG NON-CODING RNAS AND INTEGRATED STRESS IN CANCER]
- [DNA AND RNA MEDICINE]
APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining
Sara De Bragança 1, Clara Aicart-Ramos 1, Raquel Arribas-Bosacoma 2, Angel Rivera-Calzada 3, Juan Pablo Unfried 4, Laura Prats-Mari 5, Mikel Marin-Baquero 1, Puri Fortes 6, Oscar Llorca 7, Fernando Moreno-Herrero 8
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.
Keywords: APLF; CP: Molecular biology; DNA ligase IV; Ku70-Ku80; NHEJ; XLF; Xrcc4; lncRNA; magnetic tweezers; non-homologous end joining; single-molecule.
CITA DEL ARTÍCULO Cell Rep. 2022 Dec 31;42(1):111917. doi: 10.1016/j.celrep.2022.111917.
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