Checkpoint signaling: Epigenetic events sound the DNA strand‐breaks alarm to the ATM protein kinase
Abstract
The ATM protein kinase is centrally involved in the cellular response to ionizing radiation (IR) and other DNA double‐strand‐break‐inducing insults. Although it has been well established that IR exposure activates the ATM kinase domain, the actual mechanism by which ATM responds to damaged DNA has remained enigmatic. Now, a landmark paper provides strong evidence that DNA‐strand breaks trigger widespread activation of ATM through changes in chromatin structure.1 This review discusses a checkpoint activation model in which chromatin perturbations lead to the conversion of inactive ATM domains to phosphorylated, active ATM monomers. The new findings underscore the critical importance of epigenetic events in genome function and surveillance in mammalian cells. BioEssays 25:627–630, 2003.Keywords
This publication has 16 references indexed in Scilit:
- PI3K-Related Kinases: Roles in Cell-Cycle Regulation and DNA Damage Responses2003
- ATP Activates Ataxia-Telangiectasia Mutated (ATM) in VitroJournal of Biological Chemistry, 2003
- ATM and related protein kinases: safeguarding genome integrityNature Reviews Cancer, 2003
- Memory by modification: the influence of chromatin structure on gene expression during vertebrate developmentGene, 2003
- DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociationNature, 2003
- The fundamental role of epigenetic events in cancerNature Reviews Genetics, 2002
- Cell cycle checkpoint signaling through the ATM and ATR kinasesGenes & Development, 2001
- ATM and ATR: networking cellular responses to DNA damageCurrent Opinion in Genetics & Development, 2001
- Cell Cycle Checkpoints: Preventing an Identity CrisisScience, 1996
- When is a lipid kinase not a lipid kinase? When it is a protein kinaseCell, 1995