Abstract: Provided are compositions, systems, and methods that employ one or more fusion protein pairs, wherein each fusion protein within a fusion protein pair comprises a sequence-specific nucleic acid binding protein, such as sequence-specific Cas9 protein (e.g., a CRISPR), a sequence specific transcription activator-like enhancer (“TALE”) protein, a sequence specific homing endonuclease (“HE”; a/k/a meganuclease), a three prime exonuclease (“TREX”), and/or a sequence specific zinc finger (“ZF”) protein, which sequence-specific nucleic acid binding protein is operably linked to one half of a split-reporter molecule, such as a split-fluorescent reporter molecule, a split-luminescent reporter molecule, a Förster resonance energy transfer (FRET) reporter molecule, or a Bioluminescence Resonance Energy Transfer (BRET) reporter molecule.