Maintaining genome integrity is an essential task of all cells, and imperfect repair of the damaged genome is responsible for a myriad of human diseases, ranging from aggressive cancers to defective immune systems. As a postdoc coadvised by Taekjip Ha and Bin Wu, I broadly explore the biophysical processes involved in DNA repair in living human cells. To achieve this goal, I developed a “very fast CRISPR” system that can induce double-strand DNA breaks (DSB) with unprecedented spatiotemporal control and specificity. vfCRISPR is a powerful enabling technique, akin to the “channelrhodopsins” in optogenetics, which permits ultrafast perturbation and subsequent interrogation of many physical and chemical processes during DSB repair. For example, this rapidly inducible CRISPR system can reveal the molecular interplay at the DSB junction, addressing how the kinetics of chromatin state switch, recruitment of repair factors, and noncoding RNA species determines DNA repair pathway choices and cell fate decision. Our studies provide valuable strategies and information complementary to traditional steady-state biochemical approaches.