Figure 6

Model of feedback inhibition of retrotransposition. In healthy cells, L1 expression is regulated by several mechanisms, but on occasion one or more of these mechanisms can be disrupted, such as loss of methylation induced repression of the L1 promoter associated with early tumorigenesis (A). This loss of regulation of L1 expression is a greatly deleterious condition for cells (B). Cells adapt to constitutive L1 expression by more rapidly repairing double stranded breaks (C). We propose that this increased speed of repair results both in the inhibition of L1 and Alu retrotransposition, and a reduced sensitivity to transient L1 expression (D). Lightning bolts represent toxicity associated with transient L1 expression. Their size represents the relative magnitude of this toxicity. Cells appear green to represent the deleterious nature of L1 open reading frame (ORF)2 expression. Darker shades of green represent cells experiencing greater levels of L1 ORF2-associated toxicity.