Figure 8. Model describing TRF1 as a negative regulator of telomeric transcription (TERRAs), APBs formation, telomeric recombination via PolD3-BIR dependent pathway.

Replicative stress induced by TRF1 deletion alters the chromatin status of these telomeres. Recruitment of chromatin remodellers/HR factors, TERRA accumulation and telomere fragility are observed. The SMC5/6 complex and polymerase POLD3 are among the factors recruited at replicative-stressed telomeres, representing the key players for APBs formation and telomere recombination, particularly BIR-mechanism. We propose that increased TERRAs molecules at telomeres could lead to increased R-loops, which are bypassed by POLD3 dependent BIR to resolve fork progression hindrance.