Alternative Lengthening of Telomeres: DNA Repair Pathways Converge.

Alternative Lengthening of Telomeres: DNA Repair Pathways Converge. Trends Genet. 2017 Sep 29;: Authors: Sobinoff AP, Pickett HA Abstract Telomeres shorten during each cellular division, with cumulative attrition resulting in telomeric damage and replicative senescence. Bypass of replicative senescence precipitates catastrophic telomere shortening or crisis, and is characterized by widespread genomic instability. Activation of a telomere maintenance mechanism (TMM) is necessary to stabilise the genome and establish cellular immortality through the reconstitution of telomere capping function. The alternative lengthening of telomeres (ALT) pathway is a TMM frequently activated in tumors of mesenchymal or neuroepithelial origin. ALT is a homology-directed recombination-dependent replication pathway that utilizes telomeric templates for synthesis; however, its precise protein requirements have remained elusive. Recently, several developments have shed light on the DNA repair pathways that become engaged at ALT telomeres, implicating ALT telomeres as DNA repair hot spots. Here, we review recent discoveries regarding the ALT mechanism, and discuss how DNA repair pathways converge to maintain the length and functional integrity of telomeres in ALT cancers. PMID: 28969871 [PubMed - as supplied by publisher]
Source: Trends in Genetics : TIG - Category: Genetics & Stem Cells Authors: Tags: Trends Genet Source Type: research