Related Experiment Video
Updated: Aug 11, 2026
11:04
RNA Next-Generation Sequencing and a Bioinformatics Pipeline to Identify Expressed LINE-1s at the Locus-Specific Level
Published on: May 19, 2019
The human LINE-1 retrotransposon creates DNA double-strand breaks
Stephen L Gasior1, Timothy P Wakeman, Bo Xu
1Tulane Cancer Center and Department of Epidemiology, Tulane University Health Sciences Center, 1430 Tulane Ave., New Orleans, LA 70112, USA.
Journal of Molecular Biology
|February 24, 2006
Summary
Long interspersed element-1 (L1) retrotransposons cause DNA double-strand breaks (DSBs) during human genome activity. The DNA repair protein ATM is essential for repairing these L1-induced DSBs and for L1 insertion.
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- Long interspersed element-1 (L1) are autonomous retroelements active in the human genome.
- L1 insertion mechanism requires double-strand break (DSB) formation in genomic DNA.
- The role of DNA repair pathways in L1 retrotransposition is not fully understood.
Purpose of the Study:
- To investigate the DNA damage response to L1 expression in mammalian cells.
- To determine the role of the ATM DNA repair protein in L1-induced DSBs and retrotransposition.
- To characterize the efficiency of L1 integration into the host genome.
Main Methods:
- Immunolocalization of gamma-H2AX foci to detect DSBs.
- COMET assay for DNA strand break analysis.
- Assessing L1 retrotransposition efficiency in the presence and absence of ATM.
Main Results:
- L1 expression induces a high level of DSBs, evidenced by gamma-H2AX foci and COMET assay.
- ATM is required for the formation of L1-induced gamma-H2AX foci.
- ATM is essential for L1 retrotransposition, indicating a host DNA repair gene requirement for integration.
- L1-induced DSBs significantly exceed successful insertion events, highlighting integration inefficiency.
Conclusions:
- L1 retrotransposition triggers a significant DNA damage response, characterized by DSB formation.
- The host DNA repair protein ATM plays a critical role in both repairing L1-induced DSBs and facilitating L1 integration.
- Endogenous L1 endonuclease activity may contribute to genomic instability through DSB induction in germline and somatic tissues.
Related Concept Videos
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
02:04Fixing Double-strand Breaks
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
02:04Fixing Double-strand Breaks
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
03:08LTR Retrotransposons
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant in mammals compared to other class I transposable elements. About 8 percent of human genomic DNA comprises LTR retrotransposons. Some of the common examples of LTR retrotransposons are Ty elements in yeast and Copia elements in Drosophila.
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...
The internal coding region of LTR retrotransposons and their mechanism of transposition closely resembles a...