CDK6 regulates expression of integrator complex genes and replication proteins through activation of the cell cycle because cycling is associated with replicative stress of the genome.

We propose that nuclear transcriptional dynamics at the DNA, at breakpoints, at points of nascent transcription, at points of repair and at the points of replication stress, will reflect synchronization of the many enzymatic requirements of faithful DNA replication and repair with the kinetics and timing of the cell cycle and a successful division of the cell. We present here an experimental construct to evaluate this concept, the interplay between the cyclin-dependent kinase CDK6 and a set of nuclear proteins active at the DNA during replication or repair: RPA1/2 and the INTS integrator complex proteins, to illustrate that which we term here transcriptional homeostasis essentially and effectively translates to genomic stability.