CDK2 inhibition plays a central role in DNA damage–induced cell cycle arrest and DNA repair. However, whether CDK2 also influences early porcine embryo development is unknown. In this study, we examined whether CDK2 is involved in the regulation of oocyte meiosis and early embryonic development of porcine. We found that disrupting CDK2 activity with RNAi or an inhibitor did not affect meiotic resumption or MII arrest. However, CDK2 inhibitor-treated embryos showed delayed cleavage and ceased development before the blastocyst stage. Disrupting CDK2 activity is able to induce sustained DNA damage as demonstrated by the formation of distinct γH2AX foci in nuclei of day 3- and day 5-embryos. Inhibiting CDK2 triggers a DNA damage checkpoint by activating of the ATM-P53-P21 pathway. However, the mRNA expression of genes involved in non-homologous end-joining (NHEJ) or homologous recombination (HR) pathways for double strand break (DSB) repair reduced after administering CDK2 inhibitor to 5-day-old embryos. Furthermore, CDK2 inhibition caused apoptosis in day 7 blastocysts. Thus, our results indicate that an ATM-P53-P21 DNA damage checkpoint is intact in the absence of CDK2; however, CDK2 is important for proper repair of the damaged DNA by either directly or indirectly influencing DNA repair-related gene expression.

• HaiYang Wang(Department of Animal Sciences, Chungbuk National University, Brain Korea 21 center for Bio-Resource Development, Chungbuk National University, South Korea)
• Yu-Jin Jo(Department of Animal Sciences, Chungbuk National University, Brain Korea 21 center for Bio-Resource Development, Chungbuk National University, South Korea)
• Tian-Yi Sun(Department of Animal Sciences, Chungbuk National University, Brain Korea 21 center for Bio-Resource Development, Chungbuk National University, South Korea)
• Suk Namgoong(Department of Animal Sciences, Chungbuk National University, Brain Korea 21 center for Bio-Resource Development, Chungbuk National University, South Korea)
• Xiang-Shun Cui(Department of Animal Sciences, Chungbuk National University, Brain Korea 21 center for Bio-Resource Development, Chungbuk National University, South Korea)
• Jeong Su Oh(Department of Genetic Engineering, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea)
• Nam-Hyung Kim(Department of Animal Sciences, Chungbuk National University, Brain Korea 21 center for Bio-Resource Development, Chungbuk National University, South Korea)