2026-04-29T17:02:14Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/230922024-11-29T23:03:26Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author De Bragança, Sara author Aicart-Ramos, Clara author Arribas-Bosacoma, Raquel author Rivera-Calzada, Angel author Unfried, Juan Pablo author Prats-Mari, Laura author Marin-Baquero, Mikel author Fortes, Puri author Llorca Blanco, Oscar Antonio author Moreno-Herrero, Fernando funder Ministerio de Ciencia, Innovación y Universidades (España) funder Unión Europea funder Consejo Superior de Investigaciones Científicas (España) 2024-09-16T08:17:00Z 2024-09-16T08:17:00Z 2023-01-31 Cell Rep . 2023 ;42(1):111917. 10.1016/j.celrep.2022.111917 2211-1247 Cell reports 36640344 https://hdl.handle.net/20.500.12105/23092 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. eng APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining. research article