Maximus Peto’s Commentary
From the title, this paper looked especially interesting. Reading the abstract, it seems like ALT activity was activated by a problem with DAXX, and ALT was suppressed by re-introducing a wild-type DAXX. So this intervention may only be addressing a very specific problem (with DAXX), and not capable of eliminating ALT in all cases. This may still have important relevance for understanding and addressing ALT tumors, but it may instead only be relevant for tumors that develop ALT capability from dysfunctions in DAXX.
Rapid and reversible suppression of ALT by DAXX in osteosarcoma cells.
Sci Rep. 2019 Mar 14;9(1):4544.
Yost KE, Clatterbuck Soper SF, Walker RL, Pineda MA, Zhu YJ, Ester CD, Showman S, Roschke AV, Waterfall JJ, Meltzer PS
PubMed publication date (edat): 3/16/2019
Many tumors maintain chromosome-ends through a telomerase-independent, DNA-templated mechanism called alternative lengthening of telomeres (ALT). While ALT occurs in only a subset of tumors, it is strongly associated with mutations in the genes ATRX and DAXX, which encode components of an H3.3 histone chaperone complex. The role of ATRX and DAXX mutations in potentiating the mechanism of ALT remains incompletely understood. Here we characterize an osteosarcoma cell line, G292, with wild-type ATRX but a unique chromosome translocation resulting in loss of DAXX function. While ATRX and DAXX form a complex in G292, this complex fails to localize to nuclear PML bodies. We demonstrate that introduction of wild type DAXX suppresses the ALT phenotype and restores the localization of ATRX/DAXX to PML bodies. Using an inducible system, we show that ALT-associated PML bodies are disrupted rapidly following DAXX induction and that ALT is again restored following withdrawal of DAXX.
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418139/