Fig. 1
From: Novel therapeutic strategies targeting telomere maintenance mechanisms in high-risk neuroblastoma
Mechanisms underlying the relationship between ATRX loss of function and ALT. Diagram of (a) a normal and (b) an ALT telomere. In normal cells ATRX and H3.3 co-localise with telomeric DNA, within PML bodies [23]. Following ATRX LoF, MRN complexes co-localise with PML bodies and a failure of telomeric H3.3 deposition results in G-quadruplex formation, facilitating non-canonical homologous recombination mechansims. Additionally, in the absence of functional ATRX, TERRA binds to telomeric DNA, facilitaing the formation of DNA-RNA hybrids known as R-loops which also promote homologous recombination repair