ANALYSIS OF CDK2 FUNCTION DURING MEIOSIS

Abstract

Cyclin-dependent kinase 2 (CDK2) is an absolute requirement for meiotic division. In mouse models lacking CDK2 or CDK2-associated activity, germ cell development is arrested during prophase I of the first meiotic division. In this thesis, I investigate whether CDK2 shows functionality as a transcriptional regulator during meiotic division. My major findings demonstrate that CDK2 can bind the chromatin of male germ cells undergoing meiosis. By CDK2 ChIPseq I show that this occurs due to the association of CDK2 with the nuclear respiratory factor (NRF1) transcription factor. I also demonstrate that CDK2-mediated phosphorylation of NRF1 within its DNA binding domain and has an inhibitory effect on its transcriptional activity and that CDK2 deletion leads to differential expression of NRF1 target genes. I propose that this novel CDK2-NRF1 interaction, may regulate NRF1 transcriptional activity during meiosis and this regulatory role may also be important for germ cell development.