1. Cellular Aging and Genome Stability
Aging starts at the cellular level and shares many commonalities with cancer such as increased DNA damage. Age is the number one predisposing factor for a cancer diagnosis yet most work in DSB repair has been performed in young cells, immortalized cancer cells, or in young model organisms.
Emerging research from our laboratory shows that the recruitment of HR and NHEJ repair factors to a DSB change during aging. HR declines and there is a shift towards the usage of end-joining mechanisms and a progressive increase in the frequency of repair products with an MMEJ signature.
2. Nej1 in DSB repair pathway choice and MMEJ
There are two main pathways of DSB repair, homologous recombination (HR) and non-homologous end joining (NHEJ). There is also a third DSB repair pathway called microhomology mediated end-joining (MMEJ), which was first identified as an alternative end-joining (alt-EJ) pathway used when the two canonical pathways were disrupted.
Most repair factors are recruited to a DSB before a particular pathway has been specified. Nej1, like human XLF, is a core NHEJ factor important for DSB end-bridging. Nej1 functions at the crossroads of NHEJ and MMEJ, and repair pathway choice in general.
3. Modeling premature aging and cancer-relevant mutations in budding yeast
This is area of research in our laboratory is broad. We have ongoing projects investigating
1. RecQ helicases, 2. The Smc5/6 complex, and 3. Dyskerin. Disruption in these factors lead to premature aging and cancer in humans and are highly conserved in yeast.