The ATRX gene contains the SNF2/SWI2-related “helicase” domains and has ATP-dependent chromatin remodeling activity. ATRX ranks 17th on Davoli et al.’s list of tumor suppressors (100), taking into account the nature of the mutations as well as gene length, ratios of silent to nonsilent mutations, and other features likely to predict tumor suppressor activity. It is mutated in about 40% of low-grade gliomas, 20% of pancreatic cancers, 10% of small cell lung cancers, and 9% of uterine endometrial cancers. ATRX cooperates with DAXX to insert the histone variant H3.3 into chromatin and hence appears to function within a histone chaperon complex (101). Mutations in ATRX cause a syndrome characterized by anemia (actually α-thalassemia) and mental retardation, and are encoded on the X chromosome (102). However, since its discovery, it has been implicated in telomere function, DNA methylation, and sister chromatid cohesion and congression. The 280-kD protein includes an unusual N-terminal PHD designated the ATRX-DNMT3-DNMT3L (ADD) domain, owing to its similarity to a protein region found in the DNA methyltransferases (DNMTs). However, the relationship of this domain to its role in
