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From yeast to humans: Understanding the biology of DNA Damage Response (DDR) kinases

The DNA Damage Response (DDR) is a complex network of biological processes that protect cells from accumulating aberrant DNA structures, thereby maintaining genomic stability and, as a consequence, preventing the development of cancer and other diseases. The DDR pathway is coordinated by a signaling...

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Detalles Bibliográficos
Autores principales: Cussiol, José Renato Rosa, Soares, Bárbara Luísa, de Oliveira, Francisco Meirelles Bastos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade Brasileira de Genética 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198005/
https://www.ncbi.nlm.nih.gov/pubmed/31930279
http://dx.doi.org/10.1590/1678-4685-GMB-2019-0071
Descripción
Sumario:The DNA Damage Response (DDR) is a complex network of biological processes that protect cells from accumulating aberrant DNA structures, thereby maintaining genomic stability and, as a consequence, preventing the development of cancer and other diseases. The DDR pathway is coordinated by a signaling cascade mediated by the PI3K-like kinases (PIKK) ATM and ATR and by their downstream kinases CHK2 and CHK1, respectively. Together, these kinases regulate several aspects of the cellular program in response to genomic stress. Much of our understanding of these kinases came from studies performed in the 1990s using yeast as a model organism. The purpose of this review is to present a historical perspective on the discovery of the DDR kinases in yeast and the importance of this model for the identification and functional understanding of their mammalian orthologues.