Perpetuation of a species requires that the genome be protected from endogenous and exogenous threats. Nowhere is this more critical than in the germ cells, the precursors of egg and sperm. Defects in the vigilance pathways lead to loss of genome integrity and subsequent miscarriage and/or deterioration of offspring vigor. Detailed studies of a newly identified, highly conserved genetic factor called germ cell nuclear acidic peptidase (GCNA), will provide novel insights into key determinants of genome integrity and fertility.
Our preliminary data show that loss of GCNA creates genomic instability in both Drosophila and C. elegans, indicating conservation of function. We are working on research that will provide some of the first insights into the shared mechanisms by which conserved GCNA family members promote genomic integrity and fertility across species.
To explore the mechanisms underlying gcna functions in germ cell maintenance, we are studying:
- The classes of transposable elements that are activated in the mutant, their contribution to mutation accumulation, and the potential role of small RNA pathways.
- DNA repair pathways that require gcna function.
- The role of gcna in stability of repetitive elements.
- The contribution of gcna to cell cycle regulation using state-of-the-art imaging.
- The domain structure of GCNA
- GCNA's functional relevance to human fertility and germ cell tumors.