ATRX and DAXX: Mechanisms and Mutations.

Abstract

Recent genome sequencing efforts in a variety of cancers have revealed mutations and/or structural alterations in ATRX and DAXX, which together encode a complex that deposits histone variant H3.3 into repetitive heterochromatin. These regions include retrotransposons, pericentric heterochromatin, and telomeres, the latter of which show deregulation in ATRX/DAXX-mutant tumors. Interestingly, ATRX and DAXX mutations are often found in pediatric tumors, suggesting a particular developmental context in which these mutations drive disease. Here we review the functions of ATRX and DAXX in chromatin regulation as well as their potential contributions to tumorigenesis. We place emphasis on the chromatin remodeler ATRX, which is mutated in the developmental disorder for which it is named, α-thalassemia, mental retardation, X-linked syndrome, and at high frequency in a number of adult and pediatric tumors.

• Authors: Michael A Dyer, Zulekha A Qadeer, David Valle-Garcia, Emily Bernstein
• Journal: Cold Spring Harbor perspectives in medicine (Cold Spring Harb Perspect Med) Vol. 7 Issue 3 (Mar 01 2017) ISSN: 2157-1422 [Electronic] United States
• PMID: 28062559 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Co-Repressor Proteins
• DAXX protein, human
• Histones
• Molecular Chaperones
• Nuclear Proteins
• ATRX protein, human
• X-linked Nuclear Protein

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Adult
• Animals
• Child
• Chromatin Assembly and Disassembly (genetics)
• Co-Repressor Proteins
• Disease Models, Animal
• Histones (metabolism)
• Humans
• Mental Retardation, X-Linked (genetics)
• Mice
• Molecular Chaperones
• Mutation
• Neoplasms (genetics)
• Nuclear Proteins (genetics)
• Telomere
• X-linked Nuclear Protein (genetics)
• alpha-Thalassemia (genetics)