Chromosomal rearrangements and instability caused by the LINE-1 retrotransposon.

ABSTRACT: LINE-1 (L1) retrotransposition is widespread in many cancers, especially those with a high burden of chromosomal rearrangements. However, whether and to what degree L1 activity directly impacts genome integrity is unclear. Here, we apply whole-genome sequencing to experimental models of L1 expression to comprehensively define the spectrum of genomic changes caused by L1. We provide definitive evidence that L1 expression frequently and directly causes both local and long-range chromosomal rearrangements, small and large segmental copy-number alterations, and subclonal copy-number heterogeneity due to ongoing chromosomal instability. Mechanistically, all these alterations arise from DNA double-strand breaks (DSBs) generated by L1-encoded ORF2p. The processing of ORF2p-generated DSB ends prio

SUBMITTER: Mendez-Dorantes C 

PROVIDER: S-EPMC11702581 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature