An Important Role for CDK2 in G1 to S Checkpoint Activation and DNA Damage Response in Human Embryonic Stem Cells

摘要: A precise understanding of mechanisms used by human embryonic stem cells (hESCs) to maintain genomic integrity is very important for their potential clinical applications. The G1 checkpoint serves protect and prevents with damaged DNA from entering S-phase. Previously, we have shown that downregulation cyclin-dependent kinase 2 (CDK2) in hESC causes arrest, loss pluripotency, upregulation cell cycle inhibitors p21 p27 differentiation toward extraembryonic lineages. In this study, investigate detail the role CDK2 cellular processes, which are crucial maintenance stability such as activation, repair, apoptosis. Our results suggest triggers through activation ATM-CHK2-p53-p21 pathway. Downregulation able induce sustained damage elicit response (DDR) evidenced formation distinct γ-H2.AX RAD52-BRCA1 foci nuclei. high apoptosis at early time points; however, gradually decreased overtime DDR initiated. mass spectrometry analysis does interact a large number proteins involved key processes replication, progression, chromatin modeling, thus, suggesting orchestrating fine balance between proliferation, death, repair hESC. STEM Cells 2011;29:651–659