In this manuscript, the authors have identified that CCNI binds to CDK6 and they have investigated the functions of the CDK6-CCNI complex in cell lines. They find that CCNI has similar effects than CyclinD.

Overall, the experiments have been done well and the data is interesting. Nevertheless, it is not clear if this data changes the view of the cell cycle unless the differences between CCNI and CyclinD would be better understood.
There are a number of shortcomings and issues that need to be addressed:

1- Overall, the authors should present their view of the functions of CCNI in comparison to CyclinD. In other words, what do the result really mean in the big picture of the cell cycle?
2- The authors should use conditions, where it is has been shown that CyclinD is really important. For example, cell cycle entry after serum starvation or similar experiments (the literature is full of them). In addition, they should silence CyclinD1 and then investigate the functions of CCNI (of course the inverse experiment is needed as control).
3- Fig.1f: the result from the biosensor is not convincing and it is hard to believe that this is result is significant. On top of that there are always questions about the specificity of the biosensor.
4- Some of the result in Fig.2 are not really significant and it is not clear what we learn from these.
5- The E2F target genes that are mentioned are not really the ones that are best known. Can the authors look at the most important E2F target genes?
6- It has been reported that p27 enhances the interaction between CDK4/6 and CyclinD. Maybe this is something the authors could take advantage, especially since they mention that CDK4 is a weak binder for CyclinD…