We have shown that persistent double-stranded DNA breaks (DSBs) can drive the formation of (and associate with) LINC complexes, leading to mechanical connections between DSBs inside the nucleus and microtubules in the cytoplasm (Swartz et al., 2014). This association promotes repair by homologous recombination. We continue to investigate how subnuclear compartmentalization impacts DSB repair mechanism and efficiency. We are also actively investigating the impact of the LINC complex on telomere maintenance.
Chromatin and Nuclear Mechanics
In order to investigate how chromatin contributes to nuclear mechanics in a quantitative manner, we have established methods to apply force spectroscopy to isolated S. pombe nuclei in collaboration with the laboratory of Simon Mochrie Ph.D. (Physics). Using an optical trap, we can induce repeated rounds of compression and extension and extract quantitative information about the mechanical properties of nuclei.
Nuclear Compartmentalization and Adaptation
Repetitive DNA elements are found at the nuclear envelope in yeast model systems. We are investigating how association of repetitive elements with the inner nuclear membrane contributes to genome integrity. Our data suggest that the nuclear periphery attenuates recombination between repetitive elements under normal growth conditions while cellular stress leads to a release of repetitive elements to the nuclear interior. We are developing and testing a model in which regulated association of repetitive DNA with the nuclear periphery can favor genome stability or genome adaptability, depending on the environment.