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. 2020 Jun 19;48(13):7197–7217. doi: 10.1093/nar/gkaa287

Figure 9.

Figure 9.

Schematic showing how MoTeR insertions can promote re-organization of the genome interior. (A) End-deprotection. If a MoTeR inserts in a plain telomere at a position more than three TTAGGG repeats distal to the telomere boundary, this generates a fragile site. Subsequent breakage would result in the creation of a de-protected end. Alternatively, end de-protection could occur directly via telomere cleavage by the site-specific endonuclease in the MoTeR reverse transcriptase, without a subsequent reverse transcription step. If repair is initiated before the remaining telomere repeats are lost through replicative attrition, or enzymatic resection, the ends could be repaired by telomere ‘healing’ (i), or by ectopic invasion of homologous sequences on a sister chromatid or another chromosome end (ii). In the case shown, the donor telomere possesses a MoTeR insertion, resulting in MoTeR acquisition (ii). Delayed repair could result in loss of subterminal sequences through attrition/resection, resulting in the generation of a ‘naked,’ recombinogenic end and, possibly, extensive terminal sequence loss. These naked ends can be repaired by de novo telomere formation (iii), non homologous end-joining (NHEJ) (iv), or break-induced replication (BIR) - if the free end has homology to another chromosomal sequence (v). (B) MoTeR array ‘activation.’ Breaks at interstitial telomeres constituting MoTeR-MoTeR junctions can be repaired via healing (vi); BIR using other MoTeR arrays as templates, resulting in array extensions (or contractions) (vii). Alternatively, the free end can invade the same DNA strand, forming a D-loop, with the end being extended by BIR (viii). Finally, attrition/resection of the new terminus will produce a free end comprising internal MoTeR sequences (a truncated MoTeR). This can be repaired via de novo telomere addition (ix), BIR (x), or NHEJ (xi). Note that NHEJ will result in the internalization of the truncated version of a formerly telomeric MoTeR. We refer to these internalized elements as MoTeR ‘relics.’