Project 2   

Functional analysis of FEN1 nuclease in genome stability
The project was funded by NCI to test a hypothesis that subtle deficiency or defects in the individual biochemical activities of FEN1 may lead to different phenotypes in yeast and different susceptibilities in the human population to environmental stresses and individual differences in the onset of genetic diseases.

Figure above: E160D FEN1 mice are highly susceptible to cancers as a result of their mutator phenotype and chronic inflammation. The panel shows the chronic inflammation and Tumorigenesis in the lung. Top, disease incidence at specific life stages (timeline in months) of wild-type (WT), Fen1ED/+ (ED/+) and Fen1ED/ED (ED/ED) mice. Below, histology (H&E) of normal lung, lung with chronic inflammation, adenoma and adenocarcinoma in ED/ED mice. From: Zheng et al., 2008 Nature Medicine.