Molecular cell diary system

A cell comprising, incorporated into the cell's genome, the following constructs:

• i) a nucleic acid encoding a first sequence specific nuclease (a first DNA cutter) capable of creating a double strand break (DSB) in a sequence specific manner at a first predefined constitutively accessible target site in the genomic DNA;
• ii) a nucleic acid encoding a first DNA polymerase (a first DNA writer), wherein the first DNA writer is a template-independent DNA polymerase capable of adding a random DNA sequence directly to the genomic DNA at the DSB created by the first DNA cutter in the absence of a template;
• iii) a nucleic acid encoding a second sequence specific nuclease (a second DNA cutter) that creates a second DSB in a second sequence specific manner at a second predefined constitutively accessible target site in the genomic DNA;
• and
• iv) a nucleic acid encoding a second DNA polymerase (a second DNA writer), wherein the second DNA writer is a template-dependent polymerase that is able to add a second DNA sequence directly to the genomic DNA at the second DSB created by the second DNA cutter,
• wherein, the nucleic acid encoding the first DNA cutter and the nucleic acid encoding the first DNA writer are under the control of a first promoter, wherein the first promoter is not constitutively active and is regulated during a cell cycle, by a cellular timing signal, by a cell fate transition, or by production in the cell of a first biomolecule such that expression of the first DNA cutter and the first DNA writer linked to the first promoter occurs when the first promoter is activated;
• and
• wherein the nucleic acid encoding the second DNA cutter and the nucleic acid encoding the second DNA writer are under the control of a second promoter, wherein the second promoter is not constitutively active and is regulated during a cell cycle, by a cellular timing signal, by a cell fate transition, or by production in the cell of a second biomolecule such that expression of the second DNA cutter and the second DNA writer linked to the second promoter occurs when the second promoter is activated.