Disease mutant analysis identifies a new function of DAXX in telomerase regulation and telomere maintenance

Abstract

Most human cancers depend on the telomerase to maintain telomeres; however, about 10% of cancers are telomerase negative and utilize the alternative lengthening of telomeres (ALT) mechanism. Mutations in the DAXX gene have been found frequently in both telomerasepositive and ALTcells, and how DAXX mutations contribute to cancers remains unclecions that are located in different regions of DAXX differentially impact on its ability to interact with its binding partners and its targeting to Cajal bodies and telomeres. In addition, DAXX knockdown by RNA interference led to reduced telomerase targeting to telomeres and telomere shortening. These findings collectively support a DAXXcentric pathway for telomere maintenance, where DAXX interaction with the telomerase regulates telomerase assembly in Cajal bodies and telomerase targeting to telomeres.