DNA re-replication

Cyclin-dependent kinase 2

Cyclin D

Origin recognition complex

S phase

Cancer research

Cyclin E1

DNA damage

Cyclin-dependent kinase complex

Genome instability

Biology

Gene

Kinase

Pre-replication complex

Cyclin E

Cell biology

Protein kinase A

Control of chromosome duplication

Cyclin-dependent kinase

Cell cycle

DNA replication

DNA replication factor CDT1

Cyclin A

Cyclin A2

Genetics

Eukaryotic DNA replication

Frontiers in Cell and Developmental Biology

DNA replication must be precisely controlled in order to maintain genome stability. Transition through cell cycle phases is regulated by a family of Cyclin-Dependent Kinases (CDKs) in association with respective cyclin regulatory subunits. In normal cell cycles, E-type cyclins (Cyclin E1 and Cyclin E2, CCNE1 and CCNE2 genes) associate with CDK2 to promote G1/S transition. Cyclin E/CDK2 complex mostly controls cell cycle progression and DNA replication through phosphorylation of specific substrates. Oncogenic activation of Cyclin E/CDK2 complex impairs normal DNA replication, causing replication stress and DNA damage. As a consequence, Cyclin E/CDK2-induced replication stress leads to genomic instability and contributes to human carcinogenesis. In this review, we focus on the main functions of Cyclin E/CDK2 complex in normal DNA replication and the molecular mechanisms by which oncogenic activation of Cyclin E/CDK2 causes replication stress and genomic instability in human cancer.

Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability