Alternative Lengthening of Telomeres

Often, this is due to a telomerase enzyme being reactivated, but alternative mechanisms also occur.

In proposed models for how BITS works, the process begins with the resection of a damaged telomere end: one of the strands is cut away to provide a single strand of DNA (the Guanosine-rich strand) that can bind to into a matching (homologous) template, forming a so-called displacement loop (D-loop) (Figure 1a).

After D-loop formation, DNA polymerase δ extends the invaded G-strand end, copying material beyond the original breakpoint, leading to initiation of lagging strand synthesis of the C-strand, also by DNA polymerase δ.

This is different from normal 'semi-conservative' DNA replication, where one strand is newly synthesized, and the other comes from the original template.

Recent work suggests that ALT DNA copying (BITS) proceeds via a D-loop migration model, which is supported by the observation of non-conservative rather than semi-conservative products of break-induced replication at ALT telomeres[5] and the D-loop-shaped products observed in two-dimensional gel electrophoresis at sites undergoing BIR.

Mechanisms of Alternative Lengthening of Telomeres by a recombination based mechanism. (a) Schematic of conservative replication of DNA by break-induced telomere synthesis. (b) Four potential sources of DNA/telomere sequence that can be copied during new telomere synthesis by ALT [ 1 ]