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

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...

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Autores principales:	Rafaela Fagundes, Leonardo K. Teixeira
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	cyclin E CCNE CDK2 DNA replication replication stress genomic instability Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/415ffa212bc14af29646c80254339041
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id	oai:doaj.org-article:415ffa212bc14af29646c80254339041
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spelling	oai:doaj.org-article:415ffa212bc14af29646c802543390412021-11-30T18:11:54ZCyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability2296-634X10.3389/fcell.2021.774845https://doaj.org/article/415ffa212bc14af29646c802543390412021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.774845/fullhttps://doaj.org/toc/2296-634XDNA 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.Rafaela FagundesLeonardo K. TeixeiraFrontiers Media S.A.articlecyclin ECCNECDK2DNA replicationreplication stressgenomic instabilityBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cyclin E CCNE CDK2 DNA replication replication stress genomic instability Biology (General) QH301-705.5
spellingShingle	cyclin E CCNE CDK2 DNA replication replication stress genomic instability Biology (General) QH301-705.5 Rafaela Fagundes Leonardo K. Teixeira Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability
description	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.
format	article
author	Rafaela Fagundes Leonardo K. Teixeira
author_facet	Rafaela Fagundes Leonardo K. Teixeira
author_sort	Rafaela Fagundes
title	Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability
title_short	Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability
title_full	Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability
title_fullStr	Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability
title_full_unstemmed	Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability
title_sort	cyclin e/cdk2: dna replication, replication stress and genomic instability
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/415ffa212bc14af29646c80254339041
work_keys_str_mv	AT rafaelafagundes cyclinecdk2dnareplicationreplicationstressandgenomicinstability AT leonardokteixeira cyclinecdk2dnareplicationreplicationstressandgenomicinstability
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Cyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability

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