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The high abundance of Alu elements in the human genome creates an environment that contributes to specific form of genetic instability related to nonallelic recombination. With over 1 million copy in the human genome, Alu elements are distributed across all chromosomes providing an enormous potential for non-allelic interactions. We have been studying the mechanisms of Alu/Alu interactions in causing genomic deletions using a site-specific doublestrand break that mimics environmental damage, such as ionizing radiation, to the DNA. This damage occurs throughout the cell cycle. However, the most common form of breaks in DNA occurs by replication pausing during the S phase. H-DNA forming motifs are short DNA sequences that can form unusual structures that have been shown to cause double strand break in the DNA. Due to the abundance of Alu element and H-DNA in the human genome, we hypothesize that H-DNA can induce Alu-Alu recombination in the event where the H-DNA is located between two Alu elements and represents a good model of Sphase dependent DNA breaks. To test our hypothesis, we used the previously published Alu-Alu recombination system, cloning the H-DNA sequence between either identical or mismatch Alu elements in the system. Our results indicate that H-DNA stimulates Alu-Alu recombination in both the identical system and the mismatch system when compared to the control group without H-DNA. Furthermore, cells carrying the H-DNA in the mismatch Alu-Alu recombination system show a significant shift in their repair pathway from Alt-NHEJ to Alu-Alu recombination. These data indicate a strong link between H-DNA and chromosomal instability associated with Alu-Alu recombination and demonstrate that cell cycle, among other factors, has a major influence on the nature of genetic instability caused by Alu elements.

Publication Date

2021

City

New Orleans

Keywords

H-DNA, Alu-Alu, Recombination

Disciplines

Biology | Laboratory and Basic Science Research | Life Sciences

H-DNA structure stimulates Alu-Alu Recombination

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