The makings of TERRA R-loops at chromosome ends

Telomeres protect chromosome ends from nucleolytic degradation, uncontrolled recombination by DNA repair enzymes and checkpoint signaling, and they provide mechanisms for their maintenance by semiconservative DNA replication, telomerase and homologous recombination. The telomeric long noncoding RNA TERRA is transcribed from a large number of chromosome ends. TERRA has been implicated in modulating telomeric chromatin structure and checkpoint signaling, and in telomere maintenance by homology directed repair, and telomerase - when telomeres are damaged or very short. Recent work indicates that TERRA association with telomeres involves the formation of DNA:RNA hybrid structures that can be formed post transcription by the RAD51 DNA recombinase, which in turn may trigger homologous recombination between telomeric repeats and telomere elongation. In this review, we describe the mechanisms of TERRA recruitment to telomeres, R-loop formation and its regulation by shelterin proteins. We discuss the consequences of R-loop formation, with regard to telomere maintenance by DNA recombination and how this may impinge on telomere replication while counteracting telomere shortening in normal cells and in ALT cancer cells, which maintain telomeres in the absence of telomerase.

Automated summary

Telomeres play a crucial role in protecting chromosome ends and maintaining their integrity through mechanisms such as semiconservative DNA replication, telomerase, and homologous recombination. The long noncoding RNA TERRA is involved in modulating telomeric chromatin structure and checkpoint signaling, particularly in response to damaged or short telomeres. R-loop formation and its regulation by shelterin proteins can impact telomere maintenance by DNA recombination, potentially influencing telomere replication in normal cells and ALT cancer cells.