ALT control, delete: FANCM as an anti-cancer target in Alternative Lengthening of Telomeres
Julienne J O'Rourke, Rohan Bythell-Douglas, Elyse A Dunn, Andrew J Deans
Nucleus | TAYLOR & FRANCIS INC | Published : 2019
Break-induced replication is a specific type of DNA repair that has a co-opted role in telomere extension by telomerase-negative cancer cells. This Alternative Lengthening of Telomeres (or 'ALT') is required for viability in approximately 10% of all carcinomas, but up to 50% of the soft-tissue derived sarcomas. In several recent studies, we and others demonstrate that expression and activity of FANCM, a DNA translocase protein, is essential for the viability of ALT-associated cancers. Here we provide a summary of how and why FANCM depletion leads to deletion of ALT-controlled cancers, predominantly through a hyper-activation of break-induced replication. We also discuss how FANCM can and has..View full abstract
Awarded by National Health and Medical Research Council
This work was supported by the National Health and Medical Research Council [GNT1139099]; National Breast Cancer Foundation (Australia); Victorian Cancer Agency.