ATRX/DAXX: Guarding the Genome against the Hazards of ALT

Proliferating cells must enact a telomere maintenance mechanism to ensure genomic stability. In a subset of tumors, telomeres are maintained not by telomerase, but through a homologous recombination-based mechanism termed Alternative Lengthening of Telomeres or ALT. The ALT process is linked to mutations in the ATRX/DAXX/H3.3 histone chaperone complex. This complex is responsible for depositing non-replicative histone variant H3.3 at pericentric and telomeric heterochromatin but has also been found to have roles in ameliorating replication in repeat sequences and in promoting DNA repair. In this review, we will discuss ways in which ATRX/DAXX helps to protect the genome, and how loss of this complex allows ALT to take hold.

Automated summary

Proliferating cells need a telomere maintenance mechanism for genomic stability. In some tumors, telomeres are maintained through an alternate lengthening mechanism called ALT, which is associated with mutations in the ATRX/DAXX/H3.3 histone chaperone complex. This complex is responsible for histone deposition and has roles in replication and DNA repair. This review will discuss the protective role of ATRX/DAXX in the genome and how its loss facilitates ALT.