Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division

In most mammals, the cell cycle kinase cyclin-dependent kinase 2 (CDK2) is expressed as two major isoforms as a result of alternative splicing. The shorter CDK2 isoform, CDK2S, is expressed constitutively during the cell cycle and can be detected in several tissues. In contrast, the longer isoform, CDK2L, shows preferential expression in meiotically dividing cells and upon S-phase entry in the mitotic cycle. Both CDK2L and CDK2S form heteromeric complexes with cyclins A2 and E1 in vitro. However, complexes composed of each isoform differ considerably in their kinase activity towards known CDK substrates. It is currently unknown whether the long and short isoforms of CDK2 play functionally different roles in vivo during either mitotic or meiotic divisions as conventional knockout methodology deletes both of the isoforms. Therefore, we generated mice expressing only CDK2S or CDK2L and found that both CDK2L and CDK2S are sufficient to support both mitotic and meiotic division when expressed in the absence of the other. These data contribute to the explanation of the apparent tolerance of the evolutionary loss of CDK2L expression in humans.