Studying the Human Mobile Element LINE‐1

Abstract

Long interspersed element‐1 (LINE‐1) is a 6kb long transposable element making up 17% of the human genome. LINE1 is the only currently active autonomous retro element within the human genome. LINE‐1 uses a copy and paste method to retrotranspose itself in the genome. Within the LINE‐1 mobile element are two open reading frames (ORF). ORF1 codes for a protein that acts as a chaperone and ORF2 codes for a protein that has both endonuclease and a reverse transcriptase function. Studies characterizing LINE1 endonuclease function demonstrated that LINE1 endonuclease activity induces formation of double‐stranded breaks (DSBs). Only a small fraction of LINE1‐induced DSBs results in a retrotransposition event, suggesting that the damage from the LINE1 endonuclease activity may be greater than previously considered. While LINE1 mutagenic insertion events have been associated with diseases such as breast and colon cancer as well as muscular dystrophy, the full effect of LINE1 endonuclease upon stability of the genome is undetermined. Our lab has identified inhibitors of the LINE‐1 endonuclease to elucidate the contribution of the LINE‐1 endonuclease associated DNA damage to the onset or progression of diseases such as cancer. Our lab has cell lines containing an inducible LINE‐1 at a single locus. By inserting an inducible LINE1 element integrated at a single locus we will investigate the effectiveness of our inhibitor in cells with various levels of LINE‐1 expression.Support or Funding InformationThe Louisiana Cancer Research Consortium, the NIH‐RCMI grant #8G12MD007595‐04, and NIH‐NIGMS BUILD Grant TL4GM118968, 5RL5GM118966This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.