A new function of DAXX at telomeres

The core telomerase complex, comprising the catalytic subunit TERT and the RNA template TERC, is essential for preventing the loss of genetic information from chromosomes; it specifically adds telomeric repeat sequences to their 3′ end during replication. Cancer cells often upregulate TERT to promote cell growth and proliferation. However, some cancers do not express telomerase and instead use the alternative lengthening of telomeres (ALT) mechanism, a homologous recombination-based pathway. Mutations in the DAXX gene are often found in these cells, but the role of DAXX in cancer is not clear. Wenbin Ma, Zhou Songyang and colleagues found that DAXX mutations also occur in telomerase-positive cancers, indicating that it might be involved in telomerase activity. In their work on page 331, the authors now systematically analyse these DAXX disease mutations, as well as investigating the role of endogenous DAXX. They show that endogenous DAXX localises to Cajal bodies (sites of telomerase assembly), interacts with the telomerase holoenzyme and is required for its targeting to telomeres. Accordingly, different DAXX disease mutations differentially affect DAXX localisation and function. Moreover, knockdown of endogenous DAXX results in telomere shortening, further supporting a key role for DAXX in telomere maintenance. This function of DAXX at telomeres is independent of its previously described role in the ALT pathway and could explain how DAXX dysfunction contributes to observed cancer phenotypes.