Our genome is enriched with parasites, also known as transposons, whose activation drives aging and causes diseases, such as cancer. Researchers from Duke University’s Department of Pharmacology and Cancer Biology have uncovered how these parasites replicate in host cells. Assistant professor Dr. Zhao Zhang (ZZ) and his team published their findings in Nature:
“Retrotransposons hijack alt-EJ for DNA replication and eccDNA biogenesis”
Retrotransposons are abundant genetic elements constituting about 38% of human DNA. These elements can ‘copy and paste’ themselves to keep writing the host DNA, bringing one layer of genome dynamics to shape the host biology. It has been known for decades that retrotransposons can convert their mRNA into double-stranded DNA. However, a significant knowledge gap existed regarding how this process was accomplished. The study by ZZ’s lab fills this gap, discovering that retrotransposons use the factors in the alt-EJ DNA repair process to produce circular DNA and facilitate their replication. These findings not only improve our understanding of the retrotransposon life cycle but also have implications for taming these parasites to improve human health.
This work was supported by grants to ZZ from the Pew Biomedical Scholars Program and the National Institutes of Health (DP5 OD021355 and R01 GM141018). The ZZ Lab continues to explore how transposons and circular DNA lead to genome dynamics, aiming to bring new modalities for cancer therapy.