Genome Integrity and Programmed DNA Elimination
Genome integrity is essential to life, and genome instability is often associated with aging, cancer, and other diseases. A notable exception to genome integrity is programmed DNA elimination (PDE), where a large portion of DNA is lost during development. While PDE is found in diverse organisms, its molecular detail remains poorly understood.
The Wang Lab studies PDE in nematodes, including the human parasite Ascaris. Recently, they discovered one function of PDE is to split chromosomes, leading to karyotype changes that benefit both the germline and somatic cells. This work, led by postdoctoral researcher Ryan Simmons, was published in Current Biology. In another study, graduate student Brandon Estrem used END-seq and discovered that PDE in Ascaris requires resection of DNA double-strand breaks. The resection facilitates neotelomere formation that heals the DNA breaks. This process is specific to PDE, as outlined in their recent publication in Nucleic Acids Research.
The Wang Lab is also developing new models to study PDE. Work led by research associate Tom Dockendorff established a free-living nematode as a genetic model for PDE. This work was published in Current Biology. Overall, the ongoing work on PDE in the Wang Lab is promising to provide novel insights into genome stability and maintenance.