DNA Damage and L1 Retrotransposition

[摘要] Barbara McClintock was the first to suggest that transposons are asource of genome instability and that genotoxic stress assisted intheir mobilization. The generation of double-stranded DNA breaks(DSBs) is a severe form of genotoxic stress that threatens theintegrity of the genome, activates cell cycle checkpoints, and, insome cases, causes cell death. Applying McClintock's stresshypothesis to humans, are L1 retrotransposons, the most activeautonomous mobile elements in the modern day human genome,mobilized by DSBs? Here, evidence that transposable elements,particularly retrotransposons, are mobilized by genotoxic stressis reviewed. In the setting of DSB formation, L1 mobility may beaffected by changes in the substrate for L1 integration, the DNArepair machinery, or the L1 element itself. The review concludeswith a discussion of the potential consequences of L1 mobilizationin the setting of genotoxic stress.

[学科分类] 基础医学