Author:
Fagundes Rafaela,Teixeira Leonardo K.
Abstract
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.
Funder
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Subject
Cell Biology,Developmental Biology
Cited by
53 articles.
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