Figure 2.

Model for FANCM function at ALT telomeres. (A) In FANCM-proficient ALT cells, FANCM association with telomeric chromatin assures unwinding of harmful telR-loops through its ATPase activity. Additionally, FANCM interaction with RMI1/2 assures regulated recruitment and activity of BLM. In this situation, ATRS is maintained below toxic levels allowing telomere elongation and infinite cell proliferation. In FANCM, lysine K117 and the MM2 motif are indicated by a dotted black line and a blue line, respectively. (B) In FANCM-deficient ALT cells, telR-loops accumulate and BLM is aberrantly recruited and activated, leading to excessive ATRS and eventually cell death. RMI1/2 and TOP3A are blurred to indicate that their recruitment to telomeres has not been tested yet in FANCM-deficient cells.