Abstract
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.
Highlights
Despite its apparent stability, DNA can undergo significant changes in its structure
The DNA Damage Response (DDR) pathway is coordinated by a signaling cascade mediated by the phosphatidylinositol 3-kinases (PI3K)-like kinases (PIKK) ATM and ATR and by their downstream kinases CHK2 and CHK1, respectively
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
Summary
From yeast to humans: Understanding the biology of DNA Damage Response (DDR) kinases. José Renato Rosa Cussiol , Bárbara Luísa Soares and Francisco Meirelles Bastos de Oliveira2 1Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil. 2Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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