TERRA R-loops trigger a switch in telomere maintenance towards break-induced replication and PRIMPOL-dependent repair

ABSTRACT: TERRA long non-coding RNAs associate with telomeres post transcription through base-pairing with telomeric DNA forming R-loop structures. TERRA regulates telomere maintenance but its exact modes of action remain unknown. Here, we induce TERRA transcription and R-loop formation in telomerase-expressing cells and determine that TERRA R-loop formation requires non-redundant functions of the RAD51 DNA recombinase and its enhancer RAD51AP1. TERRA R-loops interfere with semiconservative DNA replication, promoting telomere maintenance by a homology-directed repair (HDR) mechanism known as break-induced replication (BIR), which ensures telomere maintenance in ALT cancer cells. In addition, TERRA induces PRIMPOL-dependent repair, which can initiate DNA synthesis de novo downstream of replication ob

SUBMITTER: Suna In 

PROVIDER: S-SCDT-10_1038-S44318-025-00502-4 | biostudies-other |

REPOSITORIES: biostudies-other