Cyclin E deregulation and genomic instability

Abstract

Precise replication of genetic material and its equal distribution to daughter cells are essential to maintain genome stability. In eukaryotes, chromosome replication and segregation are temporally uncoupled, occurring in distinct intervals of the cell cycle, S and M phases, respectively. Cyclin E accumulates at the G1/S transition, where it promotes S phase entry and progression by binding to and activating CDK2. Several lines of evidence from different models indicate that cyclin E/CDK2 deregulation causes replication stress in S phase and chromosome segregation errors in M phase, leading to genomic instability and cancer. In this chapter, we will discuss the main findings that link cyclin E/CDK2 deregulation to genomic instability and the molecular mechanisms by which cyclin E/CDK2 induces replication stress and chromosome aberrations during carcinogenesis.